A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Occupational Therapy. Johannesburg, 2017. / Introduction Appropriate motor coordination is a prerequisite for most occupational tasks (Summers, et al., 2008) (Case-Smith & O'Brian, 2010). Young children develop motor coordination over a period of years (Case-Smith & O'Brian, 2010) (Gallahue, et al., 2012). This can be observed in the development of gross motor skills such as jumping, hopping, skipping etc. (Case-Smith & O'Brian, 2010). Delays in the development of motor coordination can thus have an effect on a child’s development in all other aspects of their life (Gallahue, et al., 2012). Problem There is a need in South Africa for a cost-effective standardised tool to evaluate motor coordination in children in a valid and reliable way. Currently standardised tools must be imported from the United States of America (USA) or the United Kingdom (UK) and may not be suitable for South African children. An evaluation tool for motor coordination does exist in South Africa, but its current scoring depends in part on the experience and skill set of the professional to judge the quality of movement during a movement task and its psychometric properties have not been explored. Aim This study aimed to identify salient behavioural characteristics that separate children with typical motor coordination development and mild to severe motor coordination dysfunction from each other on the items of the Clinical Observations of Gross Motor Items (COGMI) (SAISI, 2004), in order to provide recommendations to improve the reliability and standardization of the scoring of this tool in the 5 year 0 months – 5 years 11 months age group. Method A quantitative, comparative, descriptive, cross-sectional study design was used, with a total of 23 children in this age group. The participants were divided into a typical motor coordination (green) group and a mild to severe motor coordination dysfunction (red) group. They were videoed while performing 15 of the 18 items of the COGMI. These video recordings were analysed using movement analysis to determine specific behaviours which identify function and dysfunction in this age group. Results From the observations which could be seen when using the COGMI, clusters could be identified. As the COGMI focuses on coordination of movement rather than postures, the starting and finishing position were discarded and further analysis was only done on the movement component of items. The observations made during the movement portion of items on the COGMI were divided into observations made of the upper limbs, the lower limbs, head, neck and core. Comparisons were made between the two groups and looked at the salient behavioural characteristics that determine function and dysfunction in the age group of five year old children. Conclusion Throughout this study it was very clear that this specific age group presents with a lot of variability due to the fact that they are still developing in their gross motor skills and are not yet proficient in fundamental skills. Using these characteristics a checklist of behaviours was developed, which can be used in combination with the COGMI scoring sheet. / MT2017

Estudos mostram que a coordenação motora (CM) melhora com o passar do tempo e apresenta relação com os níveis de atividade física (AF), mas ainda não se sabe como essa relação muda ao longo do tempo. O objetivo deste estudo foi investigar a relação entre essas duas variáveis e a sua mudança em crianças dos sete aos 10 anos de idade, mediante um método longitudinal de pesquisa. A amostra constou de escolares de três projetos que receberam auxílio financeiro do Edital Universal do CNPq. O objetivo central desses projetos foi avaliar diferentes aspectos do crescimento físico, desenvolvimento motor, atividade física e aptidão física de crianças e adolescentes de seis a 14 anos de idade, da Rede de Ensino da cidade de Muzambinho - MG. Das 5 coortes constituídas, o presente estudo analisou os dados de 87 crianças (45 meninos e 42 meninas) da coorte de 7 anos, coletados dos sete aos 10 anos de idade. A CM foi medida com a bateria de testes motores KTK e a AF por meio do questionário de Godin e Shepard. Foram analisadas as mudanças normativas das duas variáveis ao longo do tempo. Para a análise da relação entre elas e a sua mudança no período estudado foram constituídos subgrupos com base no valor mediano do grupo em cada variável, ou seja, combinando-se crianças com CM alta e baixa e crianças com AF alta e baixa em cada avaliação. Os resultados normativos mostraram que o desempenho da CM melhorou ao longo do tempo e o da AF se manteve. Não se observou associação entre os níveis de CM e AF em nenhuma das avaliações. Os resultados da mudança na relação entre os níveis de CM e AF não mostraram nenhum padrão específico. Esses resultados permitem inferir que a relação entre a CM e a AF necessita levar em consideração não apenas o nível de AF, mas também a sua adequação no que se refere ao desenvolvimento da CM / Studies show that motor coordination (MC) improves over time and it presents a correlation with levels of physical activity (PA), but it is not yet known how this relationship changes over time. The objective of this study was to investigate the relationship between these two variables and the change of this relationship in children from seven to 10 years of age using a longitudinal method of research. The sample consisted of school children from three research projects that received financial support from the Edital Universal Program of CNPq. The main objective of these projects was to evaluate different aspects of physical growth, motor development, physical activity and physical fitness of children and adolescents six to 14 years of age, from the schools of Muzambinho - MG. The overall project comprised five cohorts, and this study analyzed data of 87 children (45 boys and 42 girls) of the seven years old cohort, collected from seven to 10 years of age. The MC was measured with a battery of motor tests KTK and PA was measured by the questionnaire of Godin and Shepard. It was analyzed the normative changes over time for both variables. For the analysis of the relationship between them and its change over time subgroups were formed based on the median value of the group in each variable, that is, combining children with MC high and low and children with high and low PA in each evaluation. The results of normative changes showed that the performance of MC improved over time and the PA´s remained. There was no association between MC and PA levels in any of the evaluations. The results of the change in the relationship between MC and PA levels over time showed no specific pattern. These results allow the inference that the relationship between MC and PA needs to take into account not only the amount of PA, but also its suitability in relation to the development of MC

Proper control of movements is critical for an animal’s survival, and requires the robust function of a number of genetic, molecular, neuronal and biomechanical processes. This dissertation describes a body of inter-related studies utilizing a diverse collection of Drosophila mutants to probe the roles individual genes play in shaping motor pattern generation. A particular emphasis is placed on describing the consequences of genetic perturbations of voltage-gated sodium, calcium and potassium ion channels (NaV, CaV, and KV respectively) on the function of neuronal circuits that drive motor behavior. Here, I describe the development of several quantitative protocols to study alterations in of walking (IowaFLI Tracker) and flight motor program activity and behavior in Drosophila mutants. These approaches were utilized to analyze the highly-stereotypic aberrant motor program associated with electroconvulsive stimulation (ECS)-induced seizure discharge activity in each hyperexcitable mutant. Several quantitative and mechanistic similarities between flight motor program activity and ECS-evoked discharges were identified, and the distinct aberrant ECS-evoked activity disclosed an electrophysiological signature of each mutation. Ion channel mutants display a diverse spectrum of neuronal excitability phenotypes that was highlighted in a novel hyperexcitable mutant, Shaker wings down (Swd), characterized by ether-induced leg shaking reminiscent of certain KV channel mutants (e.g. Shaker, KV1) is presented. Detailed analyses revealed disrupted walking and flight, correlated with neuronal hyperexcitability and aberrant action potential generation. Surprisingly, the Swd mutation site was mapped to a single amino acid in the voltage sensor region in paralytic (para, encoding the only NaV gene in Drosophila). Genetic analysis of intra-genic heteroallelic interactions amongst Swd and other identified para alleles further revealed a number of complex mechanisms underlying a wide phenotypic spectrum of altered neuronal excitability and motor pattern generation. The effects of perturbed ion channel function on motor program generation are compared with progressive alterations associated normal aging as well as neurodegeneration. A number of age-resilient and age-vulnerable circuits were identified along with circuit-function biomarkers of aging. Throughout this study, an integrative framework utilizing non-linear dimensional reduction approaches unraveled a broader perspective to visualize and quantify similarities and distinctions between discharge phenotypes across a large collection of Drosophila mutants.

The study of visually-guided reaching has been a meaningful tool to investigate sensory-motor coordination in typical development and different clinical paediatric populations. The aim of this study was to characterize the development of multi-joint reaching behaviour in children and youth, from 5 to 16 years of age, allowing us to capture changes that may occur into adolescence. Participants were 68 able-bodied children and youth, with no history of developmental, educational or social problems. A stratified recruitment strategy was used to adequately represent five age groups: I (5-6 years), II (7-8 years), III (9-10 years), IV (11-13 years) and V (14-16 years). A center-out reaching task was used as it allowed us to measure effects of limb mechanics during reaching. Different patterns of inter-segmental motions at the shoulder and elbow joints were needed to reach the different targets: flexion at both joints, extension at both joints, and a mixed-coordination pattern. Children were asked to reach quickly and accurately to 8 targets located at 45 degree intervals around the perimeter of a circle with a 6 cm radius. The development of reaching was described using non-parametric statistics. The global features of path length and total movement decreased as a function of increasing age, with less variability observed in older participants (p<0.05). This increased accuracy was explained by a significant reduction (p<0.05) in distance and direction error of the first movement component of the reach, indicative of the increasing ability of children to accurately plan movements based on an internal representation of the limb. These older children were also able to respond to the visual target more quickly (p<0.05). In general, initial direction errors and total movement time increased from a minimum for the 2-joint flexion coordination to a maximum for the mixed-coordination pattern. The magnitude of error, however, decreased as a function of age (p<0.05), and in particular for the mixed-coordination pattern (p<0.01). This center-out task is therefore considered to be responsive to observe effects of development and limb mechanics on performance. The established normative data set will provide a reference for the measures of performance in children with neurodevelopmental disorders. / Thesis (Master, Rehabilitation Science) -- Queen's University, 2009-11-30 11:29:28.718

Estudos mostram que a coordenação motora (CM) melhora com o passar do tempo e apresenta relação com os níveis de atividade física (AF), mas ainda não se sabe como essa relação muda ao longo do tempo. O objetivo deste estudo foi investigar a relação entre essas duas variáveis e a sua mudança em crianças dos sete aos 10 anos de idade, mediante um método longitudinal de pesquisa. A amostra constou de escolares de três projetos que receberam auxílio financeiro do Edital Universal do CNPq. O objetivo central desses projetos foi avaliar diferentes aspectos do crescimento físico, desenvolvimento motor, atividade física e aptidão física de crianças e adolescentes de seis a 14 anos de idade, da Rede de Ensino da cidade de Muzambinho - MG. Das 5 coortes constituídas, o presente estudo analisou os dados de 87 crianças (45 meninos e 42 meninas) da coorte de 7 anos, coletados dos sete aos 10 anos de idade. A CM foi medida com a bateria de testes motores KTK e a AF por meio do questionário de Godin e Shepard. Foram analisadas as mudanças normativas das duas variáveis ao longo do tempo. Para a análise da relação entre elas e a sua mudança no período estudado foram constituídos subgrupos com base no valor mediano do grupo em cada variável, ou seja, combinando-se crianças com CM alta e baixa e crianças com AF alta e baixa em cada avaliação. Os resultados normativos mostraram que o desempenho da CM melhorou ao longo do tempo e o da AF se manteve. Não se observou associação entre os níveis de CM e AF em nenhuma das avaliações. Os resultados da mudança na relação entre os níveis de CM e AF não mostraram nenhum padrão específico. Esses resultados permitem inferir que a relação entre a CM e a AF necessita levar em consideração não apenas o nível de AF, mas também a sua adequação no que se refere ao desenvolvimento da CM / Studies show that motor coordination (MC) improves over time and it presents a correlation with levels of physical activity (PA), but it is not yet known how this relationship changes over time. The objective of this study was to investigate the relationship between these two variables and the change of this relationship in children from seven to 10 years of age using a longitudinal method of research. The sample consisted of school children from three research projects that received financial support from the Edital Universal Program of CNPq. The main objective of these projects was to evaluate different aspects of physical growth, motor development, physical activity and physical fitness of children and adolescents six to 14 years of age, from the schools of Muzambinho - MG. The overall project comprised five cohorts, and this study analyzed data of 87 children (45 boys and 42 girls) of the seven years old cohort, collected from seven to 10 years of age. The MC was measured with a battery of motor tests KTK and PA was measured by the questionnaire of Godin and Shepard. It was analyzed the normative changes over time for both variables. For the analysis of the relationship between them and its change over time subgroups were formed based on the median value of the group in each variable, that is, combining children with MC high and low and children with high and low PA in each evaluation. The results of normative changes showed that the performance of MC improved over time and the PA´s remained. There was no association between MC and PA levels in any of the evaluations. The results of the change in the relationship between MC and PA levels over time showed no specific pattern. These results allow the inference that the relationship between MC and PA needs to take into account not only the amount of PA, but also its suitability in relation to the development of MC

Aim Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07) is an international survey tool based on parents' estimation of their child's motor coordination skills. The purpose of this study was to investigate the validity of a Swedish version of DCDQ'07 by finding out how the classification of Developmental Coordination Disorder (DCD) via DCDQ'07 is consistent with the classification of DCD via the motor impairment test, Movement ABC. MethodIn the context of a larger study, a Swedish translated version of the parent survey DCDQ'07 were sent to 4000 randomly selected families with children aged 8 - 10 years in Stockholm County. The classifications "DCD" or "NOT DCD" with cut-off values ​​of 56 (9 years) and 57 (10 years) were applied. Forty families were selected from 410 registered responses. Parents and children were invited to the Swedish School of Sport and Health Sciences for additional motor skills tests. Thirty-four children (8.5 ± 0.6 years) completed the quantitative part of the Movement ABC chosen as the standard criteria for motor performance with the 15th percentile as a criterion for DCD. Data processing was performed in IBM SPSS Statistics 19. Receiver Operator Characteristic curve (ROC) was used to determine positive criterion for DCDQ'07. The correlation analysis Spearman's Rho was used. Level of significance was set at p &lt;0.05. ResultsAt the cut-off values ​​of &lt;56 (9 years) and &lt;57 (10 years) the DCDQ'07 reached a sensitivity of 80 %, a specificity of 67 % and positive predicted value (ppv) of 50 %. The accepted consensus with Kappa was just below 0.4. Significant correlations were found between the Movement ABC and the total score of DCDQ'07 (r = - 0,61) and between the three subcomponents in DCDQ'07 and the sub-tasks of the Movement ABC, except one task. ConclusionThe Swedish version of DCDQ’07 exhibits an acceptable validity and is a useful screening instrument to identify children with suspected DCD. The test meets the requirement (80 %) to identify children with motor problems (sensitivity) and satisfy nearly requirement (70 %) for specificity, which is the ability to correctly identify children without motor problems. Cut-off values ​​between 48 and 57 are recommended, depending which groups should be investigated. Lower values ​​are recommended for clinical groups and higher for population-based studies. / Syfte och frågeställningar Developmental Coordination Disorder Questionnaire 2007 (DCDQ’07) är ett internationellt enkätverktyg som utgår från föräldrars skattning av sitt barns motorik. Syftet med studien var att undersöka validiteten i en svensk version av DCDQ’07 genom att ta reda på hur klassificeringen av Developmental Coordination Disorder (DCD) via DCDQ’07 stämmer med klassificering av DCD via motoriktestet Movement ABC. Metod I samband med en större studie skickades en svensk översatt version av föräldrarenkäten DCDQ’07 ut till 4000 slumpvis utvalda familjer med barn i åldrarna 8 ─ 10 år i Stockholms län. Klassificeringarna ”DCD” eller ”NOT DCD” med cutoff värdena 56 (9 år) och 57 (10 år) tillämpades. Bland 410 registrerade svar valdes 40 familjer ut. Föräldrar och barn bjöds in till Gymnastik- och idrottshögskolan för ytterligare motoriktest. Trettiofyra barn (8.5 ± 0,6 år) genomförde den kvantitativa delen av Movement ABC som valts som standard för motorisk förmåga med 15:e percentilen som kriterium för DCD. Databearbetning utfördes i IBM SPSS Statistics 19. Receiver- operator characteristic curve (ROC graf) användes för att fastställa positivt kriterium för DCDQ’07. För korrelationsanalys användes Spearmans Rho.  Signifikansnivån sattes till p&lt;0,05. Resultat Vid cutoff värdena &lt;56 (9 år) och &lt; 57 (10 år) i DCDQ’07 nåddes en sensitivitet på 80 %, en specificitet på 67 % och positive predicted value (ppv) på 50 %.  Den accepterade samstämmigheten med Kappa var strax under 0.4 . Signifikant korrelation påvisades mellan Movement ABC och totalpoäng på DCDQ’07 (r = - 0,61) och mellan de tre delkomponenterna i DCDQ’07 och samtliga deluppgifter i Movement ABC, förutom en uppgift.   Slutsats Den svenska versionen av DCDQ’07 uppvisar en acceptabel validitet och är ett lämpligt screeningsinstrument för att fånga upp barn med motoriska problem. Testet möter kravet (80 %) för att identifiera barn med trolig DCD (sensitivitet) och uppfyller nästan kravet (70 %) för specificitet, dvs. förmåga att korrekt identifiera barn utan problem. Cutoff värden mellan 48 och 57 rekommenderas beroende vilka grupper som skall undersökas. Lägre värden rekommenderas för kliniska grupper och högre för populationsstudier.

There has been limited investigation into the nature of specific language impairment (SLI) in adolescence, and even less investigation into speech production in SLI, particularly beyond the preschool years. Phonological output is crucial to oral expressive language, one of the characteristic areas of deficit in SLI. It was hypothesized that adolescents with SLI present with residual speech errors. Accordingly, this study investigated the presence, nature and cause of speech deficits in adolescents with persistent SLI. Adolescents aged 13.0-14.0 years with persistent SLI (n=31) were compared to typically developing (TD) peers (n=31) on an Oral Motor Evaluation (OME) and a Speech Assessment Battery (SAB), consisting of: Multisyllabic Word Repetition, Nonsense Word Repetition, Phrase Repetition, Sentence Repetition and Tongue Twisters. Tasks were analysed in terms of accuracy and the amount of effort required, to determine efficiency and automaticity of phonological output. All participants completed a battery of memory tasks and the language abilities of the SLI group were evaluated. Caregivers completed questionnaires investigating risk factors. Results indicated that adolescents with persistent SLI produced a higher number of inconsistent and context-dependent deviant speech behaviours than TD peers, involving syllable structure changes (phoneme additions/omissions), phoneme substitutions, fluency errors and repetitions/revisions. Participants with SLI also had a higher incidence of neuromotor deficits. Persistent SLI appears to relate to a multifactorial etiology, involving both genetic and early history factors. There was high comorbidity of attention deficits, with implications for resource allocation. Results were interpreted within a functional capacity viewpoint. Speech deficits are thought to contribute to a threshold effect, where even subtle deficits in one area can compromise processing in another area. Speech production in this population appears to be more resource-demanding than in TD peers, which may affect concurrent performance on linguistic and memory tasks. This hypothesis is supported by the high correlation between speech tasks and expressive syntax for SLI participants. The high incidence of speech deficits in adolescents with SLI ii has implications for research and clinical practice with individuals of all ages with SLI.

Ao longo da infância e juventude se faz importante avaliar o desempenho motor para monitorar o desenvolvimento motor e subsidiar objetivos de intervenção. Há diversos instrumentos com o intuito de avaliar o desempenho motor de bebês, crianças e jovens, porém uma questão que é apontada na literatura diz respeito a especificidade de cada instrumento quanto ao seu contexto. Diversos instrumentos de avaliação motora têm sido desenvolvidos no decorrer do tempo, e muitos destes foram elaborados para mensurar o mesmo fenômeno no âmbito motor, no entanto, tais instrumentos podem apresentar resultados distintos para um mesmo objetivo. Desta forma, torna-se importante verificar se estes instrumentos permitem fazer o mesmo diagnóstico. Com isso, o presente estudo tem como objetivo investigar a associação entre o TGMD-2 e o KTK, considerando tanto o desempenho quanto o diagnóstico. A amostra do presente estudo foi composta por 228 crianças pertencentes ao Estudo Longitudinal Misto de Crescimento e Desenvolvimento Motor de Muzambinho-MG, contrabalanceadas por sexo e idade (6 a 11 anos de idade). Foram realizadas avaliações por meio dos testes KTK e TGMD-2. A análise dos filmes foi realizada por avaliadores treinados com índice de concordância inter e intra individual acima de 85%. Os valores obtidos indicaram que tanto o desempenho quanto o diagnóstico dos testes não são associados, mesmo considerando a idade e sexo dos sujeitos. Os resultados apresentam um novo cenário sobre a questão da avaliação motora na infância e permitiram discutir aspectos sobre a complementariedade das baterias quanto ao domínio do desenvolvimento motor na infância / Throughout childhood and youth becomes important to assess motor performance to monitor the motor development and support intervention goals. There are several tools in order to evaluate the motor performance of infants, children and young people, but an issue that is reported in the literature concerns the specificity of each instrument as to its context. Several motor assessment tools have been developed over time, and many of these are designed to measure the same phenomenon under motor development, however, such instruments may present different results for the same goal. Thus, it is important to check that these instruments allow you to make the same diagnosis. Thus, the present study aims to investigate the association between TGMD-2 and the KTK, considering both performance diagnosis. The study sample consisted of 228 children belonging to the Joint Longitudinal Study on Growth and Development of Motor Muzambinho-MG, counterbalanced by sex and age (6-11 years old). Evaluations were performed through the KTK and TGMD-2 tests. The analysis of the films was carried out by trained assessors with level of inter and intra individual above 85%. The results indicate that both the performance and the diagnosis of the tests are not associated, regardless of age and gender of the subjects. The results present a new scenario on the issue of motor assessment in childhood and allowed a discussion on the complementary aspects of the batteries on the motor development of the area in childhood

O presente estudo teve como objetivo investigar a relação entre a coordenação motora (CM) e a aptidão física relacionada à saúde (APFRS) em escolares de seis a 13 anos de idade de ambos os sexos a partir das seguintes hipóteses: 1) Os resultados de desempenho bruto de CM se relacionam com os resultados brutos das provas de APFRS; 2) O quociente motor de CM se relaciona com o somatório de provas de APFRS em que os escolares são classificados como aptos; 3) Os níveis de CM avaliados pelo QM se relacionam com o somatório de provas de APFRS em que os escolares são classificados como apto; e 4) Uma classificação de CM, com base nos níveis de QM se relaciona com o estado de apto e não apto por provas de APFRS. Para tanto, 531 escolares (252 meninos e 279 meninas) alocados nos grupos etários inicial de 6-8 anos (n=175), intermediário de 9-10 anos (n=186) e avançado de 11-13 anos (n=170) foram avaliados por meio da bateria de testes KTK e Fitnessgram. Os resultados revelaram que para a hipótese 1, houve associação moderada entre os resultados de desempenho bruto de CM e os resultados brutos das provas de APFRS corrida da milha, resistência muscular abdominal, resistência muscular dos braços e flexibilidade do tronco, em todos os grupos investigados; em relação a hipótese 2 foi confirmada associação moderada entre o quociente motor de CM e a quantidade de escolares classificados como aptos por prova de APFRS apenas no grupo avançado de 11-13 anos (rô=0,32); quanto a hipótese 3 foi confirmada associação fraca entre o nível de CM e a quantidade de provas de APFRS em que os escolares eram classificados como aptos também apenas no grupo avançado de 11-13 anos de idade (rô= 0,26); e no que se refere a hipótese 4 verificou-se que não há associação entre estar classificado como dentro ou fora do esperado para CM com nenhuma das quatro provas de APFRS, em nenhum dos grupos investigados. Conclui-se que CM está associada à APFRS, mas isto depende do critério de analise utilizado para avaliar ambos os construtos / The present study aimed to investigate the relationship between motor coordination (CM) and physical fitness related to health (APFRS) of schoolchildren from 6 to 13 years of age of both sexes testing the following hypotheses: 1) Gross CM results are related to the gross results of the APFRS tests; 2) CM motor quotient is related to the sum of APFRS tests in which schoolchildren are classified as apt; 3) CM levels evaluated by QM are related to the sum of APFRS tests in which schoolchildren are classified as apt; and 4) A classification of CM based on QM levels are related to the state of apt/inapt in the APFRS tests. 531 schoolchildren (252 males and 279 females) divided into the initial age group of 6-8 years (n=175), the intermediate age group of 9-10 years (n=186), and the advanced age group of 11 -13 years (n=170) were evaluated by the KTK and the Fitnessgram battery tests. The results revealed that for hypothesis 1, there was a moderate association between the gross results of MC and the gross results of the following APFRS tests: mile run, abdominal muscular endurance, arms muscular endurance and trunk flexibility in all groups; in relation to hypothesis 2, a moderate association between CM motor quotient and the number of schoolchildren classified as apt in the APFRS test was confirmed only in the advanced age group of 11-13 years (rô = 0.32); concerning hypothesis 3, a weak association between CM level and the number of APFRS tests in which schoolchildren were classified as apt was confirmed also only in the advanced age group of 11-13 years (rô = 0.26); and in relation to hypothesis 4, being classified as expected/unexpected CM does not relate to being apt/inapt in the 4 tests of APFRS in none of the investigated groups. Therefore, it is concluded that CM is associated to APFRS but this depends on the criteria used to evaluate both constructs

Altos níveis de galactose circulantes e cerebrais são encontrados em portadores da galactosemia clássica não tratada, cujos pacientes comumente desenvolvem problemas cognitivos e motores ao longo da vida. Entretanto pouco se conhece a respeito dos mecanismos da disfunção celular e molecular responsáveis por estes sintomas. Assim, o objetivo do presente trabalho foi de investigar o efeito da injeção intracerebroventricular de galactose sobre a memória (aversiva e de reconhecimento de objetos) e a coordenação motora em ratos Wistar. Além disso, a atividade, o imunoconteúdo e a expressão gênica da acetilcolinesterase no hipocampo e córtex cerebral foram também avaliados. No cerebelo, foram medidos parâmetros histológicos (contagem de células e imunohistoquímica) e bioquímicos (imunoconteúdo de caspase-3 ativa e BDNF, atividade e imunoconteúdo da acetilcolinesterase, níveis de glutationa e sulfidrilas, bem como o índice de dano ao DNA). Ratos Wistar receberam uma injeção intracerebroventricular de galactose (4 mM) ou salina (controles) sendo esses submetidos às tarefas comportamentais e/ou decapitados em diferentes tempos (1 h, 3 h ou 24 h), logo após, o hipocampo, córtex cerebral e cerebelo foram dissecados. Os resultados mostraram que a galactose prejudicou a memória aversiva e de reconhecimento de objetos, quando injetada antes do treinamento, bem como alterou a atividade e a expressão gênica da acetilcolinesterase em hipocampo. Em relação ao comportamento motor e aos parâmetros histológicos e bioquímicos realizados no cerebelo, a administração intracerebroventricular de galactose prejudicou a coordenação motora e reduziu o número de células e a imunomarcação de neurônios e astrócitos. A galactose, também aumentou o imunoconteúdo de caspase-3 ativa, a atividade da acetilcolinesterase e o índice de dano ao DNA, bem como diminuiu o imunoconteúdo de BDNF e acetilcolinesterase e os níveis de glutationa e sulfidrilas no cerebelo. Tomados em conjunto, nossos resultados mostram que a administração intracerebroventricular de galactose prejudicou a memória e a coordenação motora. Além disso, o modelo experimental utilizado mostrou diversas alterações a nível celular e molecular, os quais podem contribuir pelo menos em parte com o entendimento da fisiopatologia da galactosemia clássica. / Non-treated patients with classical galactosemia present high levels of galactose in the bloodstream and brain. Patients usually develop cognitive and motor impairments during life. However, little is known about the cellular and molecular mechanisms responsible for these symptoms. Thus, the aim of this study was to investigate the effect of intracerebroventricular galactose injection on memory (aversive and object recognition) and motor coordination in Wistar rats. Acetylcholinesterase activity, immunocontent and gene expression were investigated in hippocampus and cerebral cortex. In the cerebellum, we performed histological (cell counting and immunohistochemistry) and biochemical (active caspase-3 immunocontent, BDNF, acetylcholinesterase activity and immunocontent, glutathione and sulfhydryl levels, as well as DNA damage index) parameters. Wistar rats received a single intracerebroventricular injection of galactose (4 mM) or saline (control). The animals performed behavioral tasks and/or were decapitated at different times (1 h, 3 h or 24 h) after injection. The hippocampus, cerebral cortex and cerebellum were dissected. The results showed that injecting galactose before training provokes impairment on aversive and object recognition memories, as well as altered the activity and gene expression of acetylcholinesterase in hippocampus. Regarding to the histological and biochemical parameters measured in the cerebellum, intracerebroventricular galactose injection impaired motor coordination, reduced the number of cells and immunostaining of neurons and astrocytes. In the cerebellum, galactose also increased active capase-3 immunocontent, acetylcholinesterase activity and DNA damage index, as well as decreased BDNF and acetylcholinesterase immunocontent, and glutathione and sulfhydryl levels. Altogether, our results show that intracerebroventricular injection of galactose impaired memory and motor coordination. Moreover, the experimental model used showed several alterations at cellular and molecular levels. These findings may contribute at least in part with the understanding of the physiopathology in classical galactosemia.