As exposições precoces às diferentes intervenções, como dietas e estresse, estão associadas a persistentes alterações sobre aspectos neuroquímicos e comportamentais, podendo este ser considerado um gatilho de transtornos psiquiátricos na vida adulta. O presente trabalho objetivou determinar se estas intervenções neonatais poderiam interagir com uma dieta deficiente em ácidos graxos poliinsaturados n-3 (n-3 PUFA), aplicados durante o desenvolvimento, com foco nos níveis centrais (hipocampo) e séricos do fator neurotrófico derivado do encéfalo (BDNF), bem como sobre a atividade enzimática e aspectos morfológicos (e.g. massa, potencial) mitocondriais do hipocampo de ratos machos adultos. Em nossa abordagem experimental animal, as ninhadas foram distribuídas aleatoriamente nos grupos intactos, manipulados neonatalmente [MN, separação mãe-filhote durante 10min/dia, entre o 1° e o 10° dia pós-natal (DPN)] e separado maternalmente [SM, separação mãe-filhote durante 3h/dia, entre o 1° e o 10° DPN]. No DPN 35, os filhotes machos foram agrupados em dieta n-3 PUFA adequada ou deficiente, por 17 semanas de tratamento. O peso e o consumo de ração foram aferidos semanalmente. Após este tratamento, soro e hipocampo foram coletados. Kits comerciais foram utilizados para a medição dos níveis hipocampais e séricos de BDNF (ELISA), bem como a atividade dos complexos da cadeia respiratória mitocondrial (método enzimático, análise espectrofotométrica), massa e potencial mitocondriais (MitoTracker, citometria de fluxo). A expressão gênica de BDNF no hipocampo também foi medido por RT-qPCR. Os testes estatísticos utilizados foram ANOVA de duas vias ou de medidas repetidas. Os níveis de significâncias foram fixados em p<0,05. A dieta deficiente em n-3 PUFA, associada aos estressores neonatais deste estudo (MN, SM) foram capazes de alterar o peso corporal e a ingestão de alimentos de um modo específico, uma vez que os níveis mais elevados destes parâmetros foram encontrados em animais submetidos a SM. Animais submetidos a MN alimentados com uma dieta n-3 PUFA deficiente exibiram uma maior atividade exploratória em resposta a um psicoestimulante (dietilpropiona). Embora os níveis proteicos séricos e hipocampais de BDNF permaneceram inalterados pelos tratamentos aplicados, fomos capazes de demonstrar a redução de sua expressão gênica em animais alimentados com uma dieta n-3 PUFA deficiente. Considerando os padrões mitocondriais e parâmetros de estresse oxidativo, as atividades das enzimas antioxidantes glutationa peroxidase (GPx) e catalase (CAT), bem como a produção de espécies reativas de oxigênio (EROs) se encontraram aumentadas no hipocampo de animais submetidos a uma deficiência crônica em n-3 PUFA. Esta deficiência mostrou interações com o fator estresse neonatal em alguns destes parâmetros (e.g. atividade da GPx, produção de EROs), indicando um possível sinergismo entre estressores neonatais e a deficiência em n-3 PUFA. Os níveis de tióis foram significativamente menores nos grupos estressados (MN, SM), sendo a dieta n-3 PUFA deficiente capaz de aumentar a quantidade de tiol no hipocampo. Por outro lado, animais estressados tratados cronicamente com uma dieta deficiente em n-3 PUFA apresentaram níveis mais elevados de tiol. Contudo, a MN per se foi capaz de diminuir o potencial mitocondrial hipocampal. Adicionalmente, um estudo com humanos teve como objetivo correlacionar os níveis de BDNF periféricos ao consumo de n-3 PUFA em adolescentes. Para este estudo, 137 adolescentes de uma amostra enriquecida para psicopatologias de ansiedade foram submetidos a um questionário de frequência alimentar (QFA), para uma análise quantitativa do consumo de macronutrientes e micronutrientes de n-3 PUFA. As correlações de Spearman foram realizadas para avaliar possíveis associações entre o consumo de n-3 PUFA e os níveis periféricos de BDNF. As amostras de sangue foram coletadas entre 7 a 10h após o período de 10-12h de jejum, sendo o soro armazenado para medir os níveis de BDNF. Todas as análises de BDNF foram realizadas no mesmo dia por ELISA, utilizando anticorpos monoclonais específicos para o BDNF, de acordo com as instruções do fabricante. Os efeitos de possíveis confundidores (e.g. consumo total de gordura, idade, sexo e medida de ansiedade) foram examinados por modelos de regressões lineares. Apesar de algumas limitações apresentadas (e.g. o tamanho reduzido da amostra, alta incidência de adolescentes ansiosos), o que poderia limitar a validade externa deste resultado, fomos capazes de detectar uma correlação entre o consumo de n-3 PUFA e os níveis séricos de BNDF em adolescentes. Como conclusão geral, esta tese demonstra que a manipulação neonatal e separação materna, associada com uma deficiência em n-3 PUFA, são capazes de alterar parâmetros comportamentais e neuroquímicos na idade adulta. Este sinergismo foi capaz de diminuir a expressão gênica de BDNF no hipocampo, embora não apresentando qualquer alteração deste parâmetro perifericamente. A correlação entre os níveis consumidos de n-3 PUFA, em uma população de adolescentes em idade escolar, com os níveis séricos de BDNF também foi encontrada. Ainda, as alterações nas atividades enzimáticas mitocondriais observadas no hipocampo destes animais reforçam a importância da participação desta estrutura, além de sua possível relação com o desenvolvimento de desordens psiquiátricas e de humor. Considerando-se a nossa abordagem metodológica em ratos, a mesma pode ser um protocolo útil para se estudarem as interações entre o ambiente precoce e a nutrição ao curso de vida em diferentes desfechos neuroquímicos. / Early exposure to different interventions, as diets and stress, are associated with persistent alterations in neurochemistry and behavior, and can be considered a trigger of psychiatric disorders in adulthood. This study investigated whether neonatal interventions interact with a diet deficient in n-3 polyunsaturated fatty acids (n-3 PUFA) applied during development, focusing on central (hippocampus) and serum brain-derived neurotrophic factor (BDNF), as well as mitochondrial enzymatic activity and morphology (e.g. mass, potential) in adult male rats. In our animal study, litters were randomized into non-handled (NH), handled [H, mother-offspring separation for 10min/day from 1st-10th postnatal day (PND)] and separated (S, separation for 3h/day from the 1st-10th PND) groups. On PND 35, male pups were randomized into adequate or deficient diet in n-3 PUFA for 17 weeks. The weight and food intake were measured weekly. Serum and hippocampi were collected after this n-3 PUFA treatment. Commercial kits were used for measuring hippocampal and serum BDNF (ELISA), as well as mitochondrial chain respirator complexes (enzymatic method, spectrophotometric analysis), mitochondrial mass and potential (MitoTracker, flow citometry). Hippocampal BDNF gene expression was also measure by RT-qPCR. Statistical testes used were Two-Way or repeated measures ANOVA. Significance levels were set at p<0.05. A n-3 PUFA deficient diet, in association with neonatal stressors used in this study (H, MS) were able to alter body weight and food intake in a specific way, since higher levels of these parameters were found in animals subjected to MS. Animals subjected to H fed an n-3 PUFA deficient diet displayed enhanced exploratory activity in response to a psychostimulant (diethylpropion). Although serum protein levels and hippocampus BDNF remained unchanged by the treatments applied, we were able to demonstrate its gene expression reduction in the hippocampus of animals fed an n-3 PUFA deficient diet. Considering mitochondrial and oxidative stress parameters, the activities of antioxidant enzymes glutathione peroxidase (GPx) and catalase (CAT) and the production of reactive oxygen species (ROS) were increased in the hippocampus of rats subjected to a deficiency n-3 PUFA. This deficiency displayed interactions with neonatal stress factor in some of these parameters (e.g. GPx activity, ROS), indicating a possible synergism between neonatal stressors and n-3 PUFA deficiency. Thiol levels were significantly decreased by neonatal stressors (H and MS), and the n-3 PUFA deficient diet was able to increase its total amount in hippocampus. On the other hand, chronically stressed animals treated with an n-3 PUFA deficient diet showed higher thiol levels. However, H per se was able to decrease mitochondrial potential in hippocampus. Additionally, a clinical study aimed to correlate peripheral BDNF levels and n-3 PUFA consumption in adolescents. For this study, 137 adolescents from a sample enriched for psychopathology of anxiety were subjected to a food frequency questionnaire (FFQ), in order for measuring the quantitative analysis of n-3 PUFA macronutrients and micronutrients consumption. Spearman correlations were performed to assess the association between n-3 PUFA consumption and serum BDNF levels. Blood samples were collected between 7 and 10h after fasting period of 10-12h, and serum was stored in order to measure BDNF levels. All BDNF measurements were performed in the same day by sandwich-ELISA using monoclonal antibodies specific for BDNF, according to the manufacturer’s instructions. Effects of potential confounders (e.g. total fat consumption, age, gender, anxiety) were examined using linear regression models. Although some limitations were presented (e.g. small sample size with high incidence of eager teenagers), which could limit the external validity of this result, we were able to detect a correlation between the consumption of n-3 PUFA and BDNF serum levels in adolescents. As a general conclusion, this thesis reports that neonatal handling and maternal separation, associated with a nutritional deficiency in n-3 PUFA, were able to change behavioral and neurochemical parameters in adulthood. This synergism was able to decrease BDNF gene expression in the hippocampus, while not presenting any change of this parameter peripherally. A correlation between the consumption levels of n-3 PUFA, in a population of schoolchildren with BDNF serum levels was also found. Still, changes in mitochondrial enzymatic activities observed in the hippocampus of these animals reinforce the importance of this structure participation and its relation to the development of psychiatric and mood disorders. Considering our rat methodological approach, it can be a useful tool for studying the interactions between early life environment and life-course nutrition on different neurochemical outcomes.

As exposições precoces às diferentes intervenções, como dietas e estresse, estão associadas a persistentes alterações sobre aspectos neuroquímicos e comportamentais, podendo este ser considerado um gatilho de transtornos psiquiátricos na vida adulta. O presente trabalho objetivou determinar se estas intervenções neonatais poderiam interagir com uma dieta deficiente em ácidos graxos poliinsaturados n-3 (n-3 PUFA), aplicados durante o desenvolvimento, com foco nos níveis centrais (hipocampo) e séricos do fator neurotrófico derivado do encéfalo (BDNF), bem como sobre a atividade enzimática e aspectos morfológicos (e.g. massa, potencial) mitocondriais do hipocampo de ratos machos adultos. Em nossa abordagem experimental animal, as ninhadas foram distribuídas aleatoriamente nos grupos intactos, manipulados neonatalmente [MN, separação mãe-filhote durante 10min/dia, entre o 1° e o 10° dia pós-natal (DPN)] e separado maternalmente [SM, separação mãe-filhote durante 3h/dia, entre o 1° e o 10° DPN]. No DPN 35, os filhotes machos foram agrupados em dieta n-3 PUFA adequada ou deficiente, por 17 semanas de tratamento. O peso e o consumo de ração foram aferidos semanalmente. Após este tratamento, soro e hipocampo foram coletados. Kits comerciais foram utilizados para a medição dos níveis hipocampais e séricos de BDNF (ELISA), bem como a atividade dos complexos da cadeia respiratória mitocondrial (método enzimático, análise espectrofotométrica), massa e potencial mitocondriais (MitoTracker, citometria de fluxo). A expressão gênica de BDNF no hipocampo também foi medido por RT-qPCR. Os testes estatísticos utilizados foram ANOVA de duas vias ou de medidas repetidas. Os níveis de significâncias foram fixados em p<0,05. A dieta deficiente em n-3 PUFA, associada aos estressores neonatais deste estudo (MN, SM) foram capazes de alterar o peso corporal e a ingestão de alimentos de um modo específico, uma vez que os níveis mais elevados destes parâmetros foram encontrados em animais submetidos a SM. Animais submetidos a MN alimentados com uma dieta n-3 PUFA deficiente exibiram uma maior atividade exploratória em resposta a um psicoestimulante (dietilpropiona). Embora os níveis proteicos séricos e hipocampais de BDNF permaneceram inalterados pelos tratamentos aplicados, fomos capazes de demonstrar a redução de sua expressão gênica em animais alimentados com uma dieta n-3 PUFA deficiente. Considerando os padrões mitocondriais e parâmetros de estresse oxidativo, as atividades das enzimas antioxidantes glutationa peroxidase (GPx) e catalase (CAT), bem como a produção de espécies reativas de oxigênio (EROs) se encontraram aumentadas no hipocampo de animais submetidos a uma deficiência crônica em n-3 PUFA. Esta deficiência mostrou interações com o fator estresse neonatal em alguns destes parâmetros (e.g. atividade da GPx, produção de EROs), indicando um possível sinergismo entre estressores neonatais e a deficiência em n-3 PUFA. Os níveis de tióis foram significativamente menores nos grupos estressados (MN, SM), sendo a dieta n-3 PUFA deficiente capaz de aumentar a quantidade de tiol no hipocampo. Por outro lado, animais estressados tratados cronicamente com uma dieta deficiente em n-3 PUFA apresentaram níveis mais elevados de tiol. Contudo, a MN per se foi capaz de diminuir o potencial mitocondrial hipocampal. Adicionalmente, um estudo com humanos teve como objetivo correlacionar os níveis de BDNF periféricos ao consumo de n-3 PUFA em adolescentes. Para este estudo, 137 adolescentes de uma amostra enriquecida para psicopatologias de ansiedade foram submetidos a um questionário de frequência alimentar (QFA), para uma análise quantitativa do consumo de macronutrientes e micronutrientes de n-3 PUFA. As correlações de Spearman foram realizadas para avaliar possíveis associações entre o consumo de n-3 PUFA e os níveis periféricos de BDNF. As amostras de sangue foram coletadas entre 7 a 10h após o período de 10-12h de jejum, sendo o soro armazenado para medir os níveis de BDNF. Todas as análises de BDNF foram realizadas no mesmo dia por ELISA, utilizando anticorpos monoclonais específicos para o BDNF, de acordo com as instruções do fabricante. Os efeitos de possíveis confundidores (e.g. consumo total de gordura, idade, sexo e medida de ansiedade) foram examinados por modelos de regressões lineares. Apesar de algumas limitações apresentadas (e.g. o tamanho reduzido da amostra, alta incidência de adolescentes ansiosos), o que poderia limitar a validade externa deste resultado, fomos capazes de detectar uma correlação entre o consumo de n-3 PUFA e os níveis séricos de BNDF em adolescentes. Como conclusão geral, esta tese demonstra que a manipulação neonatal e separação materna, associada com uma deficiência em n-3 PUFA, são capazes de alterar parâmetros comportamentais e neuroquímicos na idade adulta. Este sinergismo foi capaz de diminuir a expressão gênica de BDNF no hipocampo, embora não apresentando qualquer alteração deste parâmetro perifericamente. A correlação entre os níveis consumidos de n-3 PUFA, em uma população de adolescentes em idade escolar, com os níveis séricos de BDNF também foi encontrada. Ainda, as alterações nas atividades enzimáticas mitocondriais observadas no hipocampo destes animais reforçam a importância da participação desta estrutura, além de sua possível relação com o desenvolvimento de desordens psiquiátricas e de humor. Considerando-se a nossa abordagem metodológica em ratos, a mesma pode ser um protocolo útil para se estudarem as interações entre o ambiente precoce e a nutrição ao curso de vida em diferentes desfechos neuroquímicos. / Early exposure to different interventions, as diets and stress, are associated with persistent alterations in neurochemistry and behavior, and can be considered a trigger of psychiatric disorders in adulthood. This study investigated whether neonatal interventions interact with a diet deficient in n-3 polyunsaturated fatty acids (n-3 PUFA) applied during development, focusing on central (hippocampus) and serum brain-derived neurotrophic factor (BDNF), as well as mitochondrial enzymatic activity and morphology (e.g. mass, potential) in adult male rats. In our animal study, litters were randomized into non-handled (NH), handled [H, mother-offspring separation for 10min/day from 1st-10th postnatal day (PND)] and separated (S, separation for 3h/day from the 1st-10th PND) groups. On PND 35, male pups were randomized into adequate or deficient diet in n-3 PUFA for 17 weeks. The weight and food intake were measured weekly. Serum and hippocampi were collected after this n-3 PUFA treatment. Commercial kits were used for measuring hippocampal and serum BDNF (ELISA), as well as mitochondrial chain respirator complexes (enzymatic method, spectrophotometric analysis), mitochondrial mass and potential (MitoTracker, flow citometry). Hippocampal BDNF gene expression was also measure by RT-qPCR. Statistical testes used were Two-Way or repeated measures ANOVA. Significance levels were set at p<0.05. A n-3 PUFA deficient diet, in association with neonatal stressors used in this study (H, MS) were able to alter body weight and food intake in a specific way, since higher levels of these parameters were found in animals subjected to MS. Animals subjected to H fed an n-3 PUFA deficient diet displayed enhanced exploratory activity in response to a psychostimulant (diethylpropion). Although serum protein levels and hippocampus BDNF remained unchanged by the treatments applied, we were able to demonstrate its gene expression reduction in the hippocampus of animals fed an n-3 PUFA deficient diet. Considering mitochondrial and oxidative stress parameters, the activities of antioxidant enzymes glutathione peroxidase (GPx) and catalase (CAT) and the production of reactive oxygen species (ROS) were increased in the hippocampus of rats subjected to a deficiency n-3 PUFA. This deficiency displayed interactions with neonatal stress factor in some of these parameters (e.g. GPx activity, ROS), indicating a possible synergism between neonatal stressors and n-3 PUFA deficiency. Thiol levels were significantly decreased by neonatal stressors (H and MS), and the n-3 PUFA deficient diet was able to increase its total amount in hippocampus. On the other hand, chronically stressed animals treated with an n-3 PUFA deficient diet showed higher thiol levels. However, H per se was able to decrease mitochondrial potential in hippocampus. Additionally, a clinical study aimed to correlate peripheral BDNF levels and n-3 PUFA consumption in adolescents. For this study, 137 adolescents from a sample enriched for psychopathology of anxiety were subjected to a food frequency questionnaire (FFQ), in order for measuring the quantitative analysis of n-3 PUFA macronutrients and micronutrients consumption. Spearman correlations were performed to assess the association between n-3 PUFA consumption and serum BDNF levels. Blood samples were collected between 7 and 10h after fasting period of 10-12h, and serum was stored in order to measure BDNF levels. All BDNF measurements were performed in the same day by sandwich-ELISA using monoclonal antibodies specific for BDNF, according to the manufacturer’s instructions. Effects of potential confounders (e.g. total fat consumption, age, gender, anxiety) were examined using linear regression models. Although some limitations were presented (e.g. small sample size with high incidence of eager teenagers), which could limit the external validity of this result, we were able to detect a correlation between the consumption of n-3 PUFA and BDNF serum levels in adolescents. As a general conclusion, this thesis reports that neonatal handling and maternal separation, associated with a nutritional deficiency in n-3 PUFA, were able to change behavioral and neurochemical parameters in adulthood. This synergism was able to decrease BDNF gene expression in the hippocampus, while not presenting any change of this parameter peripherally. A correlation between the consumption levels of n-3 PUFA, in a population of schoolchildren with BDNF serum levels was also found. Still, changes in mitochondrial enzymatic activities observed in the hippocampus of these animals reinforce the importance of this structure participation and its relation to the development of psychiatric and mood disorders. Considering our rat methodological approach, it can be a useful tool for studying the interactions between early life environment and life-course nutrition on different neurochemical outcomes.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The work of agents in the socio Socio-Educational Service Centers is ruled by a high concentration, fast pace, unpredictability, great responsibilities; which can lead to constant stress. Based on the guiding question: there is an association between high psychological demands at work, low worker control over work activities and development of minor psychiatric disorders (MSD) on these agents?, This study aimed to investigate the psychosocial dimensions - control and psychological demands of work and its association with the occurrence of MPD agents of socioeducational workers of CASE/RS. The central hypothesis is that the association is positive. It is a cross-sectional study with a sample of 381 socio agents. In order to evaluate MPD and groups of the Karasek demand-control model, the Brazilian versions of the Self Report Questionnaire-SRQ-20 and Job Stress Scale - JSS were respectively applied. Data collection was performed using self-administered questionnaire in the period from March to August 2011. Data insertion was conducted using Epi-Info ®, version 6.4, with double independent typing. After checking for errors and inconsistencies, the data analysis was performed in PASW® (Predictive Analytics Software) 18.0 for Windows. To examine associations, chi-square test has been applied, Odds Ratio and its respective confidence intervals (CI 95%). Sociodemographic, employment, health habits were tested and those associated (p<0.25) both the exposure and the outcome (satisfaction with the workplace, number of agents on the scale, shift, day off work, suspicion for alcoholism, leisure time, physical and psychological activity) were tested in the multivariate models. As a result, it was found that 19.2% of socioeducational agents are in the quadrant high demand. The overall prevalence of suspicion for MPD was 50.1%. After adjusting for potential confounders, the odds of mental disorders was higher in active work quadrant (OR = 1.99, CI 95%=1.09 - 3.63), followed by high demand quadrant (OR = 2.05, IC95% = 1.03 - 4.09) compared to the agents of low demand quadrant. When the dimensions psychological demands and control are evaluated individually, both were associated with MPD. These results indicate high psychological demand, which has negative health effects of these workers, even when job control is high. In this sense, it is necessary to consider the issues of work organization in the institution, besides the planning of actions to promote health, prevent mental illness of the socio agents. / O trabalho dos agentes socioeducadores nos Centros de Atendimento Socioeducativo (CASE) é regido por alta concentração, ritmo acelerado, imprevisibilidade, grandes responsabilidades, o que pode levar a situações constantes de estresse. A partir da questão norteadora: existe associação entre altas demandas psicológicas no trabalho, baixo controle do trabalhador sobre a atividade laboral e desenvolvimento de Distúrbio Psíquico Menor (DPM) nesses agentes?, este estudo teve por objetivo investigar as dimensões psicossociais demandas psicológicas e controle do trabalho e sua associação com a ocorrência de DPM em agentes socioeducadores dos CASE/RS. A hipótese central é de que a associação é positiva. Trata-se de um estudo transversal, com uma amostra de 381 agentes socioeducadores. Para avaliação dos DPM e dos grupos do modelo demanda-Controle de Karasek, utilizaram-se as versões brasileiras do Self Report Questionnaire- SRQ-20 e Job Stress Scale JSS, respectivamente. A coleta de dados foi realizada por meio de questionário autoaplicável no período de março a agosto de 2011. Para a inserção dos dados foi utilizado o programa Epi-info®, versão 6.4, com dupla digitação independente. Após a verificação de erros e inconsistências, a análise dos dados foi realizada no PASW® (Predictive Analytics Software) 18.0 for Windows. Para verificar associações, adotaram-se o teste qui-quadrado, Odds Ratio e seus respectivos intervalos de confiança (IC95%). Variáveis sociodemográficas, laborais, e de hábitos e saúde foram testadas e aquelas associadas (p<0,25) tanto à exposição quanto ao desfecho (satisfação com o local de trabalho, número de agentes na escala, turno, dias de afastamento do trabalho, suspeição para alcoolismo, tempo de lazer, atividade física e acompanhamento psicológico) foram testadas nos modelos multivariados. Como resultado, encontraram-se 19,2% dos agentes socioeducadores no quadrante de alta exigência. A prevalência global de suspeição para DPM foi de 50.1%. Após ajustes por potenciais confundidores, a chance de distúrbios psíquicos foi maior no quadrante trabalho ativo (OR=1,99; IC95%=1,09-3,63), seguido do quadrante alta exigência (OR=2,05; IC95%=1,03-4,09), quando comparado aos agentes do quadrante baixa exigência. Ao serem avaliadas individualmente as dimensões demandas psicológicas e controle, ambas mostram-se associadas aos DPM. Esses resultados sinalizam a alta demanda psicológica, que possui efeitos negativos à saúde destes trabalhadores, mesmo quando o controle sobre o trabalho é alto. Nesse sentido, faz-se necessário refletir sobre as questões de organização do trabalho na instituição, além do planejamento de ações de promoção à saúde, a fim de prevenir o adoecimento mental dos agentes socioeducadores.

As exposições precoces às diferentes intervenções, como dietas e estresse, estão associadas a persistentes alterações sobre aspectos neuroquímicos e comportamentais, podendo este ser considerado um gatilho de transtornos psiquiátricos na vida adulta. O presente trabalho objetivou determinar se estas intervenções neonatais poderiam interagir com uma dieta deficiente em ácidos graxos poliinsaturados n-3 (n-3 PUFA), aplicados durante o desenvolvimento, com foco nos níveis centrais (hipocampo) e séricos do fator neurotrófico derivado do encéfalo (BDNF), bem como sobre a atividade enzimática e aspectos morfológicos (e.g. massa, potencial) mitocondriais do hipocampo de ratos machos adultos. Em nossa abordagem experimental animal, as ninhadas foram distribuídas aleatoriamente nos grupos intactos, manipulados neonatalmente [MN, separação mãe-filhote durante 10min/dia, entre o 1° e o 10° dia pós-natal (DPN)] e separado maternalmente [SM, separação mãe-filhote durante 3h/dia, entre o 1° e o 10° DPN]. No DPN 35, os filhotes machos foram agrupados em dieta n-3 PUFA adequada ou deficiente, por 17 semanas de tratamento. O peso e o consumo de ração foram aferidos semanalmente. Após este tratamento, soro e hipocampo foram coletados. Kits comerciais foram utilizados para a medição dos níveis hipocampais e séricos de BDNF (ELISA), bem como a atividade dos complexos da cadeia respiratória mitocondrial (método enzimático, análise espectrofotométrica), massa e potencial mitocondriais (MitoTracker, citometria de fluxo). A expressão gênica de BDNF no hipocampo também foi medido por RT-qPCR. Os testes estatísticos utilizados foram ANOVA de duas vias ou de medidas repetidas. Os níveis de significâncias foram fixados em p<0,05. A dieta deficiente em n-3 PUFA, associada aos estressores neonatais deste estudo (MN, SM) foram capazes de alterar o peso corporal e a ingestão de alimentos de um modo específico, uma vez que os níveis mais elevados destes parâmetros foram encontrados em animais submetidos a SM. Animais submetidos a MN alimentados com uma dieta n-3 PUFA deficiente exibiram uma maior atividade exploratória em resposta a um psicoestimulante (dietilpropiona). Embora os níveis proteicos séricos e hipocampais de BDNF permaneceram inalterados pelos tratamentos aplicados, fomos capazes de demonstrar a redução de sua expressão gênica em animais alimentados com uma dieta n-3 PUFA deficiente. Considerando os padrões mitocondriais e parâmetros de estresse oxidativo, as atividades das enzimas antioxidantes glutationa peroxidase (GPx) e catalase (CAT), bem como a produção de espécies reativas de oxigênio (EROs) se encontraram aumentadas no hipocampo de animais submetidos a uma deficiência crônica em n-3 PUFA. Esta deficiência mostrou interações com o fator estresse neonatal em alguns destes parâmetros (e.g. atividade da GPx, produção de EROs), indicando um possível sinergismo entre estressores neonatais e a deficiência em n-3 PUFA. Os níveis de tióis foram significativamente menores nos grupos estressados (MN, SM), sendo a dieta n-3 PUFA deficiente capaz de aumentar a quantidade de tiol no hipocampo. Por outro lado, animais estressados tratados cronicamente com uma dieta deficiente em n-3 PUFA apresentaram níveis mais elevados de tiol. Contudo, a MN per se foi capaz de diminuir o potencial mitocondrial hipocampal. Adicionalmente, um estudo com humanos teve como objetivo correlacionar os níveis de BDNF periféricos ao consumo de n-3 PUFA em adolescentes. Para este estudo, 137 adolescentes de uma amostra enriquecida para psicopatologias de ansiedade foram submetidos a um questionário de frequência alimentar (QFA), para uma análise quantitativa do consumo de macronutrientes e micronutrientes de n-3 PUFA. As correlações de Spearman foram realizadas para avaliar possíveis associações entre o consumo de n-3 PUFA e os níveis periféricos de BDNF. As amostras de sangue foram coletadas entre 7 a 10h após o período de 10-12h de jejum, sendo o soro armazenado para medir os níveis de BDNF. Todas as análises de BDNF foram realizadas no mesmo dia por ELISA, utilizando anticorpos monoclonais específicos para o BDNF, de acordo com as instruções do fabricante. Os efeitos de possíveis confundidores (e.g. consumo total de gordura, idade, sexo e medida de ansiedade) foram examinados por modelos de regressões lineares. Apesar de algumas limitações apresentadas (e.g. o tamanho reduzido da amostra, alta incidência de adolescentes ansiosos), o que poderia limitar a validade externa deste resultado, fomos capazes de detectar uma correlação entre o consumo de n-3 PUFA e os níveis séricos de BNDF em adolescentes. Como conclusão geral, esta tese demonstra que a manipulação neonatal e separação materna, associada com uma deficiência em n-3 PUFA, são capazes de alterar parâmetros comportamentais e neuroquímicos na idade adulta. Este sinergismo foi capaz de diminuir a expressão gênica de BDNF no hipocampo, embora não apresentando qualquer alteração deste parâmetro perifericamente. A correlação entre os níveis consumidos de n-3 PUFA, em uma população de adolescentes em idade escolar, com os níveis séricos de BDNF também foi encontrada. Ainda, as alterações nas atividades enzimáticas mitocondriais observadas no hipocampo destes animais reforçam a importância da participação desta estrutura, além de sua possível relação com o desenvolvimento de desordens psiquiátricas e de humor. Considerando-se a nossa abordagem metodológica em ratos, a mesma pode ser um protocolo útil para se estudarem as interações entre o ambiente precoce e a nutrição ao curso de vida em diferentes desfechos neuroquímicos. / Early exposure to different interventions, as diets and stress, are associated with persistent alterations in neurochemistry and behavior, and can be considered a trigger of psychiatric disorders in adulthood. This study investigated whether neonatal interventions interact with a diet deficient in n-3 polyunsaturated fatty acids (n-3 PUFA) applied during development, focusing on central (hippocampus) and serum brain-derived neurotrophic factor (BDNF), as well as mitochondrial enzymatic activity and morphology (e.g. mass, potential) in adult male rats. In our animal study, litters were randomized into non-handled (NH), handled [H, mother-offspring separation for 10min/day from 1st-10th postnatal day (PND)] and separated (S, separation for 3h/day from the 1st-10th PND) groups. On PND 35, male pups were randomized into adequate or deficient diet in n-3 PUFA for 17 weeks. The weight and food intake were measured weekly. Serum and hippocampi were collected after this n-3 PUFA treatment. Commercial kits were used for measuring hippocampal and serum BDNF (ELISA), as well as mitochondrial chain respirator complexes (enzymatic method, spectrophotometric analysis), mitochondrial mass and potential (MitoTracker, flow citometry). Hippocampal BDNF gene expression was also measure by RT-qPCR. Statistical testes used were Two-Way or repeated measures ANOVA. Significance levels were set at p<0.05. A n-3 PUFA deficient diet, in association with neonatal stressors used in this study (H, MS) were able to alter body weight and food intake in a specific way, since higher levels of these parameters were found in animals subjected to MS. Animals subjected to H fed an n-3 PUFA deficient diet displayed enhanced exploratory activity in response to a psychostimulant (diethylpropion). Although serum protein levels and hippocampus BDNF remained unchanged by the treatments applied, we were able to demonstrate its gene expression reduction in the hippocampus of animals fed an n-3 PUFA deficient diet. Considering mitochondrial and oxidative stress parameters, the activities of antioxidant enzymes glutathione peroxidase (GPx) and catalase (CAT) and the production of reactive oxygen species (ROS) were increased in the hippocampus of rats subjected to a deficiency n-3 PUFA. This deficiency displayed interactions with neonatal stress factor in some of these parameters (e.g. GPx activity, ROS), indicating a possible synergism between neonatal stressors and n-3 PUFA deficiency. Thiol levels were significantly decreased by neonatal stressors (H and MS), and the n-3 PUFA deficient diet was able to increase its total amount in hippocampus. On the other hand, chronically stressed animals treated with an n-3 PUFA deficient diet showed higher thiol levels. However, H per se was able to decrease mitochondrial potential in hippocampus. Additionally, a clinical study aimed to correlate peripheral BDNF levels and n-3 PUFA consumption in adolescents. For this study, 137 adolescents from a sample enriched for psychopathology of anxiety were subjected to a food frequency questionnaire (FFQ), in order for measuring the quantitative analysis of n-3 PUFA macronutrients and micronutrients consumption. Spearman correlations were performed to assess the association between n-3 PUFA consumption and serum BDNF levels. Blood samples were collected between 7 and 10h after fasting period of 10-12h, and serum was stored in order to measure BDNF levels. All BDNF measurements were performed in the same day by sandwich-ELISA using monoclonal antibodies specific for BDNF, according to the manufacturer’s instructions. Effects of potential confounders (e.g. total fat consumption, age, gender, anxiety) were examined using linear regression models. Although some limitations were presented (e.g. small sample size with high incidence of eager teenagers), which could limit the external validity of this result, we were able to detect a correlation between the consumption of n-3 PUFA and BDNF serum levels in adolescents. As a general conclusion, this thesis reports that neonatal handling and maternal separation, associated with a nutritional deficiency in n-3 PUFA, were able to change behavioral and neurochemical parameters in adulthood. This synergism was able to decrease BDNF gene expression in the hippocampus, while not presenting any change of this parameter peripherally. A correlation between the consumption levels of n-3 PUFA, in a population of schoolchildren with BDNF serum levels was also found. Still, changes in mitochondrial enzymatic activities observed in the hippocampus of these animals reinforce the importance of this structure participation and its relation to the development of psychiatric and mood disorders. Considering our rat methodological approach, it can be a useful tool for studying the interactions between early life environment and life-course nutrition on different neurochemical outcomes.

Une prise de décision inadaptée est au centre de nombreuses pathologies neuropsychiatriques, telle que la toxicomanie, mais concerne également certains sujets sains, pour lesquels les gratifications immédiates prévalent sur les conséquences à long terme. Afin de mieux comprendre les bases neuropsychologiques et neurobiologiques de la prise de décision dans un cadre normal et pathologique, les sujets sains inadaptés constituent un modèle prometteur. Une tâche de mesure de la prise de décision chez le rat (le Rat Gambling Task, RGT) a récemment été validée dans l’équipe, très similaire à l’Iowa Gambling Task chez l’homme et permettant de révéler, parmi une population saine de rats, une majorité de sujets performants, et une minorité de non performants. Ces rats persistent à choisir les options immédiates les plus récompensantes, mais associées à de fortes pénalités imprédictibles, entrainant un faible gain final. Nous avons montré que tous ces rats sont inflexibles et moins efficaces dans la qualité du caractère dirigé de l’action. Ils présentent également une motivation accrue pour les récompenses, qui dépend d’une balance complexe coût/bénéfice, étroitement liée à l’effort à fournir, à la palatabilité de la récompense mais pas à la perception de la sensation plaisante ou des besoins métaboliques. Par ailleurs, nous avons montré qu’il n’existe pas de relation directe entre les capacités de mémoire de travail et la prise de décision. Sur le plan neurobiologique, nous avons montré 1) que la qualité du caractère dirigé de l’action dépend d’une balance d’activité PL/SDM et 2) que la prise de décision dans le RGT engage différemment des structures spécifiques selon les performances dans la tâche et la cinétique d’élaboration des choix. Ainsi, le fort recrutement de l’OFC et du Nacc shell serait un marqueur de choix adaptés, alors que celui de PL/SDM serait modulé selon la rapidité à préférer les choix favorables. Le CgA, IL et l’amygdale se désengageraient lorsque les choix sont établis. Les rats non performants présentent une hypoactivité préfrontale associée à une activité persistante de l’amygdale, suggérant un contrôle cognitif préfrontal déficient, couplé à une altération dans les associations liées à la valeur des options, induisant un déficit d’acquisition et de ré-actualisation de la valeur incitative des choix. Nous avons également montré que les différences inter-individuelles dans le RGT sont associées à des différences dans le fonctionnement basal du système monoaminergique. Les rats non performants présentent notamment (1) des métabolismes DA- et 5HT-ergique plus élevés au niveau d’IL, en accord avec l’impulsivité motrice de ces rats, et/ou la moindre qualité du caractère dirigé de l’action et (2) un métabolisme DA-ergique plus élevé au niveau du Nacc core et 5HT-ergique plus faible au niveau du BLA, suggérant une relation étroite avec leur motivation accrue et la qualité des associations liées à la valeur des options. Finalement, ces données sont intéressantes au regard des modifications dans le fonctionnement monoaminergique de base induites par des polymorphismes génétiques, conduisant à une prise de décision inadaptée, ainsi qu’à certaines pathologies psychiatriques. Toutes ces caractéristiques comportementales et neurobiologiques qui forment un ensemble cohérent pourraient correspondre à un endophénotype de troubles mentaux. Les études à l’avenir devront investir la relation directe avec la pathologie, telle que l’addiction, et l’exploration de ces caractéristiques au niveau génétique. / Decision-making is profoundly impaired in several psychiatric disorders such as addiction, but also in some healthy individuals for whom immediate gratifications prevail over long term gain. To better elucidate the neuropsychological and neurobiological bases of good and poor decision making in normal and pathological conditions, healthy poor decision-makers represent a promising model. Recently, a Rat Gambling Task, aimed at measuring decision-making like in the Iowa gambling Task in humans has been validated. It allows the identification, among a normal population of rats, of majority of good decision-makers, and a minority of poor decision-makers that prefer immediate larger reward despite suffering large loses. We demonstrated that all poor decision makers are unflexible and less efficient in goal-directed behavior. They also have a higher motivation for reward that depends on a complex cost/benefice balance, related to the effort to make, to food palatability, but not to the perception of the pleasant feeling or to metabolic needs. Moreover, we demonstrated the absence of relationship between decision making performance and working memory. At the neurobiological level, we demonstrated 1) that efficiency in goal-directed behavior depends on balance of activity between PL and SDM and 2) that decision making depends on specific brain regions, with a level of activity related to the performance, as well as the time course to make choices. Higher OFC and Nacc shell activities are systematically associated with good decision making, whereas the recruitment of PL/SDM is modulated according to the time course to make good choices. CgA, IL and the amygdala would be disengaged when choices are established. Poor decision makers display a prefrontal hypoactivity associated with a persistent involvement of the amygdala, suggesting an alteration in the prefrontal cognitive control, combined with deficits in reward-based associations, leading to an impaired acquisition and/or re-updating of the incentive value of the options. Moreover, we demonstrated that inter-individual differences in the RGT are associated with distinct DA- and 5HT basal functions. Poor decision makers notably displayed (1) high DA- and 5HT-ergic metabolisms in IL, supporting their motor impulsivity and/or lower efficiency in goal-directed behavior and (2) a higher DA-ergic metabolism in the Nacc core, and lower 5HT-ergic in BLA, that could be related to their higher motivation, and the quality of reward-based associations. These data support the relationship between genetic polymorphisms inducing distinct basal monoaminergic functioning, and poor decision making as well as psychiatric disorders. All these cognitive/behavioural and neurobiological characteristics that make a consistent framework could be an endophenotype of mental disorders. Further experiments should examine the direct relationship between poor decision making and psychiatric disorders, such as addiction, and the genetic background related to this specific profile.

Neurotoxlns represent unique chemical tools, providing a means to 1) gain insight into cellular mechanisms of apopotosis and necrosis, 2) achieve a morphological template for studies otherwise unattainable, 3) specifically produce a singular phenotype of denervation, and 4) provide the starting point to delve into processes and mechanisms of nerve regeneration and sprouting. There are many other notable uses of neurotoxins in neuroscience research, and ever more being discovered each year. The objective of this review paper is to highlight the broad areas of neuroscience in which neurotoxins and neurotoxicity mechanism come into play. This shifts the focus away from neurotoxins per se, and onto the major problems under study today. Neurotoxins broadly defined are used to explore neurodegenerative disorders, psychiatric disorders and substance use disorders. Neurotoxic mechanisms relating to protein aggregates are indigenous to Alzheimer disease, Parkinson's disease. NeuroAIDS is a disorder in which microglia and macrophages have enormous import. The gap between the immune system and nervous system has been bridged, as neuroinflammation is now considered to be part of the neurodegenerative process. Related mechanisms now arise in the process of neurogenesis. Accordingly, the entire spectrum of neuroscience is within the purview of neurotoxins and neurotoxicity mechanisms. Highlights on discoveries in the areas noted, and on selective neurotoxins, are included, mainly from the past 2 to 3 years.

No description available.

The aim of this explorative study is to establish if psychiatric disorders influence the criminal capacity of child offenders. A qualitative approach was adopted in the study to develop an in-depth understanding of the issues pertaining to criminal capacity assessments for child offenders with psychiatric disorders. The risks associated with various psychiatric disorders in relation to childhood criminality, and the methods that are used to deal with child offenders who suffer from psychiatric disorders, were also explored. The data collection tool for this study was a semi-structured interview schedule. Telephonic and face-to-face interviews were conducted with child justice and mental health experts from four provinces in South Africa, namely, KwaZulu-Natal, Gauteng, Eastern Cape and Western Cape. These experts included psychiatrists, psychologists, social workers, academic professors of law, a criminologist and an advocate. Snowball sampling was employed and although this is a pure qualitative study, the open coding, axial coding and selective coding process from the grounded theory was applied to analyse and interpret the data. The findings from this study indicate that psychiatric disorders are a risk factor associated with the causation of criminal behaviour. A high prevalence of psychiatric disorders, such as intellectual disability, learning disorder, attention deficit hyperactivity disorder, oppositional defiant disorder and conduct disorder, were generally found in children in conflict with the law. The influence and consequences of these psychiatric disorders, in conjunction with environmental and societal factors, were found to influence criminal behaviour and were highlighted as factors that ought to be taken into consideration when determining the criminal capacity of a child who is in conflict with the law. Findings from the study identified that adequate recognition was not granted to the influence of a psychiatric disorder in the assessment of a child‟s criminal capacity. It was established that, in the criminal capacity assessment, the emphasis should not be on the psychiatric disorder per se, but on the effect that the disorder and associated symptoms may have on the child‟s ability to distinguish between the wrongfulness of their actions and to act in accordance with this understanding. Operational challenges and ambiguities identified in the legislative framework pertaining to child offenders with psychiatric disorders were found to negatively influence criminal capacity assessments for children in conflict with the law. The lack of services available to child offenders with psychiatric disorders, as well as child offenders without psychiatric disorders, was found to hamper the best interest of the children in conflict with the law. Lastly, legislative and service recommendations for good practice to deal with child offenders with psychiatric disorder were identified by the experts. / Criminology and Security Science / M.A. (Criminology)

This study aims to investigate how dimensionality reduction of neuroimaging data prior to training support vector machines (SVMs) affects the classification accuracy of bipolar disorder. This study uses principal component analysis (PCA) for dimensionality reduction. An open source data set of 19 bipolar and 31 control structural magnetic resonance imaging (sMRI) samples was used, part of the UCLA Consortium for Neuropsychiatric Phenomics LA5c Study funded by the NIH Roadmap Initiative aiming to foster breakthroughs in the development of novel treatments for neuropsychiatric disorders. The images underwent smoothing, feature extraction and PCA before they were used as input to train SVMs. 3-fold cross-validation was used to tune a number of hyperparameters for linear, radial, and polynomial kernels. Experiments were done to investigate the performance of SVM models trained using 1 to 29 principal components (PCs). Several PC sets reached 100% accuracy in the final evaluation, with the minimal set being the first two principal components. Accumulated variance explained by the PCs used did not have a correlation with the performance of the model. The choice of kernel and hyperparameters is of utmost importance as the performance obtained can vary greatly. The results support previous studies that SVM can be useful in aiding the diagnosis of bipolar disorder, and that the use of PCA as a dimensionality reduction method in combination with SVM may be appropriate for the classification of neuroimaging data for illnesses not limited to bipolar disorder. Due to the limitation of a small sample size, the results call for future research using larger collaborative data sets to validate the accuracies obtained. / Syftet med denna studie är att undersöka hur dimensionalitetsreduktion av neuroradiologisk data före träning av stödvektormaskiner (SVMs) påverkar klassificeringsnoggrannhet av bipolär sjukdom. Studien använder principalkomponentanalys (PCA) för dimensionalitetsreduktion. En datauppsättning av 19 bipolära och 31 friska magnetisk resonanstomografi(MRT) bilder användes, vilka tillhör den öppna datakällan från studien UCLA Consortium for Neuropsychiatric Phenomics LA5c som finansierades av NIH Roadmap Initiative i syfte att främja genombrott i utvecklingen av nya behandlingar för neuropsykiatriska funktionsnedsättningar. Bilderna genomgick oskärpa, särdragsextrahering och PCA innan de användes som indata för att träna SVMs. Med 3-delad korsvalidering inställdes ett antal parametrar för linjära, radiala och polynomiska kärnor. Experiment gjordes för att utforska prestationen av SVM-modeller tränade med 1 till 29 principalkomponenter (PCs). Flera PC uppsättningar uppnådde 100% noggrannhet i den slutliga utvärderingen, där den minsta uppsättningen var de två första PCs. Den ackumulativa variansen över antalet PCs som användes hade inte någon korrelation med prestationen på modellen. Valet av kärna och hyperparametrar är betydande eftersom prestationen kan variera mycket. Resultatet stödjer tidigare studier att SVM kan vara användbar som stöd för diagnostisering av bipolär sjukdom och användningen av PCA som en dimensionalitetsreduktionsmetod i kombination med SVM kan vara lämplig för klassificering av neuroradiologisk data för bipolär och andra sjukdomar. På grund av begränsningen med få dataprover, kräver resultaten framtida forskning med en större datauppsättning för att validera de erhållna noggrannheten.

This study aimed to develop a framework for improved legislation, methods of practice and services used to meet the best interest of child offenders with psychiatric disorders within the South African child justice system. This aim was achieved via a qualitative study, which evaluated child justice and mental health legislation, methods of practice, role-players, and services in South Africa, and compared same to those in Namibia, Botswana, and Nigeria; to establish if the best interest of child offenders with psychiatric disorders are currently met from a South African perspective. Data collection occurred in two phases: a document analysis of legislation, policies, and procedures in the selected comparative jurisdictions; followed by semi-structured interviews with child justice and mental health experts. During phase one the researcher analysed child justice and mental health legislation, human rights protections, and policy related to child justice in Nigeria, Botswana, Namibia, and South Africa. In addition, she interrogated literature relating to child justice and mental health, in comparative jurisdictions. This phase formed the foundation for the semi-structured interview schedule. Purposive and theoretical sampling was used to conduct 24 semi-structured interviews. Data was analysed and interpreted using pure qualitative document and thematic analysis. The overarching findings indicate that the best interest of child offenders with psychiatric disorders, in the South African child justice system, are unprotected. This vulnerable group is not dealt with from an individualised, case-specific, multi-disciplinary perspective; informed by legislation, practice-policy, and a service-orientated approach. Further, certain domestic legislation and methods of practice are inadequate in holistically assessing a child who comes into conflict with the law in the jurisdictions of comparison. Further findings identified that biological, psychological, environmental, cultural, and social factors influence the development of psychiatric disorders in children, which may bring them into conflict with the law. This study further confirmed that Attention Deficit Hyperactivity Disorder, Intellectual Development Disorder, Learning Disorder, Oppositional Defiant Disorder, and Conduct Disorder are prevalent in children who iv come into conflict with the law. Further, substance abuse disorder, depression and attachment disorder were identified as predominant factors affecting children who come into conflict with the law. The influence of these factors, in conjunction with biological, psychological, environmental, cultural, and social factors, were found to predispose children to psychiatric disorders linked to criminal behaviour. Thus, to meet the best interest standard; children in conflict with the law must be dealt with using a multi-factorial approach which considers biological, environmental, social, cultural, and psychological factors. In this way, the behaviour of child offenders with psychiatric disorders will be addressed holistically in a manner that considers all factors influencing behaviour. The empirical data supported the recommendations used to develop a trans-disciplinary framework for child offenders with psychiatric disorders. / Olu phononongo lwesi sifundo lujolise ekuphuhliseni isakhelo somthetho ophuculiweyo, iindlela zokusebenza kunye neenkonzo ukwenzela ukunikezela ezona zilungileyo iimfuno zabantwana abangabaphuli-mthetho benengulo yesifo sengqondo kwinkqubo yobulungisa yabantwana eMzantsi Afrika. Le njongo yaphunyezwa ngokwenziwa kwezifundo ezisemgangathweni ezahlola umthetho wobulungisa kubantwana kunye nomthetho olawula ezempilo ngokwengqondo, iindlela zokusebenza, abathathi-nxaxheba kunye neenkonzo eMzantsi Afrika. Ezi zathi ngoko zathelekiswa nomthetho, umsebenzi abathathi-nxaxheba kunye neenkonzo eNamibia, eBotswana, kunye naseNigeria ukufumanisa ukuba iimfanelo ezizizo zabantwana abangabaphuli-mthetho abaneengxaki zengqondo bayanakekelwa ngoku eMzantsi Afrika. Ukuqokelelwa kweenkcukacha kwenzeka kumanqanaba amabini: uhlalutyo lwemiqulu yomthetho, umgaqo-nkqubo kunye nenkqubo; Ukucazululwa kwamaxwebhu/kwemiqulu omthetho, umgaqo-nkqubo kunye neenkqubo ezikhethiweyo zothelekiso kulawulo lwezobulungisa, lilandelwe ludliwano-ndlebe olungahlelwanga ngokupheleleyo neengcaphephe/neengcali zezobulungisa lwabantwana kunye nemilo yezengqondo. Kwinqanaba lokuqala umphandi ucazulule umthetho wobulungisa kubantwana kunye nempilo yezengqondo, ukhuseleko lwamalungelo oluntu.kunye nemigaqo-nkqubo ehambelana/ enxulumene nobulungisa kubantwana eNigeria, eBotswana, eNamibia naseMzantsi Afrika. Ukongezelela walugocagoca uncwadi olubhekisele kubulungisa babantwana nezempilo yezengqondo kulawulo lwezobulungisa Eli nqanaba libe sisiseko soludwe lwenkqubo yodliwano-ndlebe olungamiselwanga ngokupheleleyo. Isampulu enenjongo neyingcingane yasetyenziswa ukuze kuqhutywe udliwano-ndlebe olungama-24 olungahlelwanga ngokupheleleyo. Ulwazi (idata) lwacalulwa lwacaciswa kusetyenziswa uxwebhu olusemgangathweni kunye nocalulo (analysis) olusemxholweni. Iziphumo ezicacileyo/eziqaqambileyo eziluphahla zibonisa ukuba okukokona kulungele abantwana abangabaphuli-mthetho abaneengxaki zezengqondo, abakhuselekanga kwinkqubo yezobulungisa babantwana eMzantsi Afrika. Eli qela lingakhuselekanga alivelelwa ngokomntu neengxaki zakhe yedwa, ngokwengxaki yakhe ngokuthe ngqo kusetyenziswe indlela ezahlukileyo ezilawulwa ngumthetho, ngumgaqo-nkqubo osebenzayo nokuvelela ngendlela yokuziqhelanisa nemeko. Ukuya phambili, eminye yemithetho yasekhaya neendlela zokusebenza azonelanga ekuhloleni ngokupheleleyo kumntwana ohlangabezana nokuphikisana nomthetho kummandla wothelekiso. Kuphinde kwafunyaniswa ukuba iimeko zozalo, zengqondo, zendawo, zenkcubeko nezentlalo ziyaziphembelela iingxaki zezengqondo ezivelayo ebantwaneni, ezinokwenza baphikisane nomthetho. Olu phononongo luqhubeka lungqina ukuba ukunganiki ngqalelo kwingxaki yokuphaphazela, ingxaki yokukhula kwengqiqo, ingxaki yokufunda, ingxaki yenkcaso yokulungileyo/ ukudelela kunye nengxaki yokuziphatha zixhaphakile kubantwana (abonayo) abaphikisana nomthetho. Ingxaki yokusebenzisa iziyobisi, ingcinezelo kunye nokuxhomekeka ziye zaphawulwa njengeemeko ezixhaphakileyo ezikhathaza abantwana abalwa nomthetho (abonayo). Iimpembelelo zezi meko, zidibene neemeko zozalo, zezengqondo, zendawo, zenkcubeko nezentlalo, zifunyenwe zilungiselela kwangaphambili abantwana kwezi ngxaki zezengqondo zithungelene ekuziphatheni ngokolwaphulo-mthetho. Ngoko ke ukuhlangabezana nomgangatho ofanelekileyo nobalulekileyo, ebhekelela abantwana abaphikisana nomthetho (abonayo) makusetyenzwe ngabo kusetyenziswe indlela ejongene neemeko ezininzi ezibandakanya iimeko zozalo, zendawo, zentlalo, zenkcubeko kunye nezengqondo. Ngale ndlela abantwana abaphula umthetho abanengxaki yezengqondo baya kuncedwa ngokupheleleyo ngendlela ebandakanya zonke iimeko eziphembelela ukuziphatha. Idatha ekholose ngamava avela kumava nokuboniweyo ixhasa izindululo ezenziweyo zokumisa isakhelo esisebenza kulo lonke uqeqesho lomntwana ophikisana nomthetho (owonayo) onengxaki yezengqondo. / Patlisiso ena e reretswe ho hlahisa moralo wa molao o ntlafetseng, mekgwa ya tshebetso le ditshebeletso bakeng sa molemo wa batlodi ba molao bao e leng bana ba nang le mathata a kelello tshebeletsong ya toka ya bana Afrika Borwa. Morero ona o fihletswe ka boithuto ba boleng, bo lekantseng melao ya toka ya bana le ya bophelo bo botle ba kelello, mekgwa ya tshebetso, baamehi le ditshebeletso Afrika Borwa. Tsona di ile tsa bapiswa le melao, tshebetso, baamehi le ditshebeletso dinaheng tsa Namibia, Botswana le Nigeria ho fumana hore na melemo e loketseng ya batlodi ba molao bao e leng bana ba nang le mathata a kelello e ya fumaneha hajwale Afrika Borwa. Pokeletso ya dintlha e etsahetse ka mekgahlelo e mmedi: manollo ya ditokomane tsa molao, melawana le mekgwatshebetso dibakeng tse kgethilweng tsa papiso tsa semolao; ho latetswe ke di-inthavu tse sa hlophiswang le ditsebi tsa toka ya bana le tsa molao wa bophelo bo botle ba kelello. Mokgahlelong wa pele mofuputsi o ile a manolla molao wa toka ya bana le wa bophelo bo botle ba kelello, ditshireletso tsa ditokelo tsa botho le melawana e amanang le toka ya bana dinaheng tsa Nigeria, Botswana, Namibia le South Africa. Ho feta moo, o ile a batlisisa dingolwa tse mabapi le toka ya bana le bophelo bo botle ba kelello dibakeng tse ka bapiswang tsa semolao. Mokgahlelo ona o bile motheo wa lenane la di-inthavu tse sa hlophiswang. Ho sebedisitswe mokgwa wa disampole wa kgetho le wa theho ya thiori ho etsa di-inthavu tse 24 tse sa hlophiswang. Dintlha di manollotswe le ho tolokwa ka manollo e sa tswakwang ya boleng ba ditokomane le ditema. Diphetho tse akaretsang di supa hore melemo e nepahetseng ya batlodi ba molao bao e leng bana ba nang le mathata a kelello ha e ya sireletswa moralong wa toka ya bana wa Afrika Borwa. Sehlopha sena se kotsing ha se sebetswe ka tjhebo ya bo-motho ka mong, ya kgetsi e kgethehileng, ya mafapha a mangata e tshehedistsweng ke molao, molawana wa tshebetso le tjhebo ya tshebetso. Ho feta moo, melao e meng ya lehae le mekgwa ya tshebetso e ne e fokola bakeng sa ho lekola ngwana ka tsela e felletseng, ya iphumanang a le kgahlano le molao dibakeng tsa semolao tse neng di bapiswa. ix Ho boetse ha fumanwa hore dintlha tsa tlhaho, kelello, tikoloho, setso le botjhaba di susumetso tlhaho ya bokudi ba kelello baneng, e leng ho etsang hore ba iphumane ba le kgahlano le molao. Boithuto bona hape bo tiisitse hore bokudi ba tlholeho ya tsepamiso le ketso e fetang tekano, bokudi ba kgolo ya bohlale, bokudi ba ho ithuta, bokudi ba ho ba kgahlano le ba bang le bokudi ba boitshwaro bo bongata bakeng ba iphumanang ba le kgahlano le molao. Bokudi ba tshebediso e mpe ya tahi kapa dithethefatsi, tshithabelo ya maikutlo le bokudi ba kgokahano di fumanwe e le mabaka a mantlha a amang bana ba qwaketsanang le molao. Tshusumetso ya dintlha tsena, hammoho le dintlha tsa tlhaho, kelello, tikoloho, setso le botjhaba, di fumanwe e le hore di pepesa bana ho bokudi ba mafu a kelello a amanngwang le botlokotsebe. Kahoo, e le ho ka fihlella maemo a melemo e nepahetseng, bana ba kgahlano le molao ba lokela ho sebetswa ka mokgwa wa ditsela tse fapaneng tse ngata, o kenyeletsang dintlha tsa tlhaho, tikoloho, setso, botjhaba le kelello. Ka mokgwa ona, batlodi ba molao bao e leng bana ba nang le bokudi ba kelello ba tla shejwa le ho sebetswa ka mokgwa o phethahetseng o kenyelletsang dintlha tsohle tse susumetsang boitshwaro. Dintlha tse bokelleditsweng di tsheheditse ditlhahiso tse sebedisitsweng ho hlahisa moralo wa makala a fapaneng bakeng sa batlodi ba molao bao e leng bana ba nang le bokudi ba kelello. / Criminology and Security Science / D. Phil. (Criminal Justice)