Ratos submetidos à desnutrição proteica apresentam elevada impulsividade e alterações em comportamentos de avaliação de risco no labirinto em cruz elevado (LCE). A desnutrição também pode influenciar a atividade do eixo hipotálamo-hipófise-adrenal (HPA). Alterações causadas pela desnutrição podem ser parcialmente revertidas pela estimulação ambiental; animais desnutridos e submetidos ao enriquecimento ambiental apresentaram maior locomoção e exploração no LCE, comparados com animais de mesma condição de dieta e que não foram estimulados. Demonstrou-se também que a estimulação pode influenciar os níveis de corticosterona plasmática evidenciando uma alteração da sensibilidade do eixo HPA. Este trabalho tem o objetivo de comparar, em ratos desnutridos (M) e bem nutridos (C), os efeitos do enriquecimento ambiental (E) em relação às concentrações de corticosterona plasmática, expressão de receptores de glicocorticóides (GR) no hipocampo e o desempenho no LCE aos 36 dias de idade. Ratos Wistar machos foram divididos em dois grupos de acordo com a dieta e subdivididos em subgrupos conforme a manipulação ambiental. A manipulação ambiental foi realizada no período de 8 a 35 dias (1 hora por dia). Após o teste no LCE os animais foram decapitados e tiveram o sangue coletado e o cérebro removido. Para a análise de corticosterona plasmática foi utilizada a técnica de radioimunoensaio. Para a quantificação dos receptores (GR) no hipocampo foi realizada uma análise quantitativa de expressão gênica por meio da reação em cadeia da polimerase (PCR) em tempo real. Ratos M apresentaram menor peso corporal quando comparados com os ratos C (p<0,001). Em relação ao LCE, ratos M permaneceram uma maior porcentagem de tempo [F(1,44)=9,08; p<0,01] e entraram mais [F(1,44)=9,01; p<0,01] nos braços abertos em relação a C. Animais ME apresentaram porcentagem de tempo nos braços abertos (6% ± 2%) próxima àquela dos animais CN (8% ± 2%). De acordo com a PCR em tempo real, o teste do LCE alterou a quantidade de receptores GR no hipocampo (t(10)=2,37; p<0,05) e essa adaptação ocorreu diferentemente em ratos M quando comparados com os C. Também foi possível observar que a quantidade de receptores GR após o teste do LCE é diferente entre os grupos M e ME (t(11)=4,48; p<0,05). Os dados do presente estudo sugerem que animais desnutridos se expõem a mais situações de risco que ratos bem nutridos. Quando o enriquecimento ambiental foi realizado no período crítico do desenvolvimento do sistema nervoso central observou-se um efeito de neuroproteção em relação às alterações produzidas pela desnutrição tanto na expressão de RNAm de receptores GR como no comportamento de avaliação de risco de ratos no LCE. Os dados do presente trabalho também mostraram que a desnutrição pode alterar a resposta de estresse mediada pelo eixo HPA após exposição ao teste do LCE, e que o enriquecimento ambiental possui efeito protetor em relação os efeitos da desnutrição precoce sobre a atividade deste eixo / Rats subjected to protein malnutrition have high impulsivity and changes in risk-assessment behaviors in the elevated plus maze (EPM). Malnutrition can also influence the activity of the hypothalamic-pituitary-adrenal (HPA). Changes caused by malnutrition can be partly reversed by environmental stimulation; malnourished animals subjected to environmental enrichment had higher locomotion and exploration in the EPM compared with animals of the same condition and diet that were not stimulated. It was also demonstrated that stimulation can influence plasma corticosterone levels indicating a change in sensitivity of the HPA axis. This study aims to compare, in undernourished rats (M) and well nourished (C), the effects of environmental enrichment (E) in relation to plasma concentrations of corticosterone, expression of glucocorticoid receptors (GR) in the hippocampus and performance in EPM at 36 days of age. Male Wistar rats were divided into two groups according to diet and subdivided according handling environment. The environmental manipulation was performed within 8 to 35 days (1 hour per day). After testing in the EPM animals were decapitated and had their blood drawn and the brain removed. For the analysis of plasma corticosterone it was used the radioimmunoassay technique. For quantification of the glucocorticoid receptor (GR) in the hippocampus it was performed a quantitative analysis of gene expression by polymerase chain reaction (PCR) in real time. M rats showed lower body weight compared to C rats (p<0.001). In relation to the EPM, M rats showed higher number of entries [F(1,44)=9.01, p<0.01] and remain a higher percentage of time [F(1,44)=9.08, p<0.01] in the open arms as compared to C. ME rats presented a percentage of time in the open arms (6% ± 2%) similar to that of CN animals (8% ± 2%). According to the real time PCR, the EPM test changed the quantity of GR receptors in the hippocampus (t(10)=2.37, p<0.05), and that adaptation was different in M as compared with C rats. It was also observed that the amount of GR after EPM test was different between M and ME groups (t(11)=4.48, p<0.05). Data from the present study suggest that M animals are more likely to explore risk situations than C rats. It is also suggested that environmental enrichment imposed during the critical period of central nervous system development may have neuroprotective effects in both physiological and behavioral changes produced by early protein malnutrition. The data of this work also showed that malnutrition may alter the stress response mediated by the HPA axis after exposure to the EPM test and that environmental enrichment has a protective effect against the effects of malnutrition on the functioning of that axis.

Das Ziel der Untersuchungen bestand darin, mit Hilfe objektiv messbarer Verhaltensreaktionen von Schweinen deren essentielle Ansprüche und Präferenzen zu ermitteln. Der Versuchsaufbau ermöglicht eine permanente Erfassung der Verhaltensabläufe von 22 Mastschweinen über den gesamten Haltungszeitraum. Dies erfolgt durch Anwendung einer elektronischen Identifikation, die Aufenthaltsort, -dauer und -frequenz von jedem Tier erfasst. Als Aufenthaltsorte standen den Tieren ein Bereich zur Nahrungsaufnahme, ein Bereich Ruhen und zwei Beschäftigungsbereiche zur Verfügung. Beide Futterautomaten und Tränken waren mit einer Tieridentifikation ausgestattet. Durch das sensorgestützte System konnten in den zwei Versuchen im Mittel über 6000 Datensätze je Tier erhoben werden. Der Auswertungsschwerpunkt wurde auf die Analyse von Präferenz und Nutzungsstruktur der Beschäftigungsbereiche gelegt. Als Beschäftigung standen den Schweinen Sand, eine neuartige Wühlmatte und Stroh zur Verfügung. Wühlen schien für die Tiere ein wichtiges Verhaltenselement zu sein. Die Nutzungshäufigkeit der Beschäftigung betrug 6-11 Besuche je Tier und Tag. Die potentielle Nutzungsdauer der Beschäftigungsangebote erreichte im Mittel höchstens 3,4 Stunden je Tier und Tag. Die Unterschiede zwischen den Angeboten waren signifikant. Die Individualität der Schweine ist sowohl in der Nutzungsfrequenz als auch - dauer stark ausgeprägt. Der Neuigkeitswert der Beschäftigung gewinnt mit zunehmendem Alter an Bedeutung. Durch eine Modellierung der sensorgestützt erfassten Parameter Nutzungshäufigkeit und Aufenthaltsdauer zu den Beschäftigungsangeboten ist es gelungen, eine objektive Bewertung tierindividueller Präferenz zu zwei Angeboten in einer Indexzahl zu erreichen. Unter Berücksichtigung des Adaptationsprozesses auf veränderte Umweltbedingungen im zeitlichen Verlauf kann mittels des Modells außerdem eine Aussage zur Affinität und Kompensationsmöglichkeit von Angeboten vorgenommen werden. / This study analyses individual requirements and preferences of pigs by measuring objective parameters of their behaviour. In contrary to previous approaches the generated experimental setup enabling long term investigation of 22 pigs behaviour during the whole fattening period. Using sensorbased identification of every single pig it was possible to record habitation, duration of stay and the frequency of attendance in distinct area of the facility namely feeding and drinking area, resting area as well as two areas with environmental enrichment. Furthermore two automatic feeders and the drinkers were equipped with the animal identification system. More than 6000 data sets for each animal were recorded in two independent experimental series. The evaluation focused on the analysis of both preference and utilisation of environmental enrichments such as sand, novel nuzzle mat and straw. It seemed that nuzzling turned out to be essential for the animals, as six to eleven visits per day and animal were recorded. Pigs attended to the respective elements up to 3.4 hours per day. Significant preferences for specific elements could be observed. For individual study animals both frequency and duration of stay were markedly variable. Attractiveness of novel environmental enrichments increased with increasing age of the pigs. By modelling frequency of use and duration of stay, both recorded sensor-based, it was possible to accomplish an objective analysis of the individual preference for specific offers which is represented by an index number. This number supported the results obtained by complex measurements precisely yet in a simplified manner. Taking into account the adaptation process to changing environmental conditions the generated model permits a conclusion regarding affinity and compensation of the offerings.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-05T14:03:37Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) JEFFERSON ROSA DE MENEZES.pdf: 2848766 bytes, checksum: e87a7c0a040b93eb5052a1ea902c099e (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-05T14:03:52Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) JEFFERSON ROSA DE MENEZES.pdf: 2848766 bytes, checksum: e87a7c0a040b93eb5052a1ea902c099e (MD5) / Made available in DSpace on 2017-06-05T14:03:52Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) JEFFERSON ROSA DE MENEZES.pdf: 2848766 bytes, checksum: e87a7c0a040b93eb5052a1ea902c099e (MD5) Previous issue date: 2017-02-22 / A deprivação maternal é um potente estressor na fase inicial da vida de mamíferos, ocasionando diversos déficits cognitivos que se mantêm na vida adulta. Dentre os mecanismos envolvidos nestes déficits estão o desiquilíbrio oxidativo e as alterações em determinadas proteínas, como o fator neurotrófico derivado do cérebro (do inglês Brain-Derived Neurotrophic Factor, BDNF). Estes eventos podem ocorrer em diferentes regiões do no cérebro, entre elas o hipocampo, principal região responsável pela formação e consolidação das memórias. Esta dissertação investigou os efeitos de diferentes estratégias neuroprotetoras (exercício físico, suplementação com chá verde, e, enriquecimento ambiental) nos déficits de memória advindos da deprivação maternal. Para avaliar a função mnemônica, foi utilizado um modelo animal de DM (em ratos Wistar) e os testes de reconhecimento de objetos, esquiva inibitória e labirinto aquático de Morris. Para avaliar o balanço redox hipocampal quantificamos espécies reativas de oxigênio (EROs), espécies reativas ao ácido tiobarbitúrico (TBARS), níveis de glutationa (GSH) e capacidade antioxidante total (FRAP), além disso, determinamos a atividade da enzima acetilcolinesterase e a quantificamos os níveis de BDNF. Nossos resultados demonstram que o exercício físico e o chá verde são estratégias antioxidantes eficazes de neuroproteção em um modelo de DM. Também demonstram que o enriquecimento ambiental é capaz de reverter os efeitos deletérios oriundos da DM por meio do incremento dos níveis de BDNF. Estes resultados revelam a possibilidade da utilização dessas intervenções como estratégia de neuroproteção. / Maternal deprivation is a potent stressor in the early life of mammalian, leading to several cognitive deficits that remain until adulthood. Among the mechanisms involved in these deficits are the oxidative imbalance and the alterations in some proteins, such as Brain-Derived Neurotrophic Factor (BDNF), events that can occur in different brain regions, as the hippocampus, the main region responsible for the memory formation and consolidation. This master thesis investigated the effects of different neuroprotective strategies (physical exercise, green tea supplementation, and environmental enrichment) on memory deficits related to maternal deprivation (MD). To evaluate the mnemonic function was used an animal model of MD (using Wistar rats) and the object recognition, inhibitory avoidance and Morris water maze memory tests. To evaluate hippocampal redox balance we quantified the reactive oxygen species (ROS), the thiobarbituric acid reactive species (TBARS), the glutathione levels (GSH) and the total antioxidant capacity (FRAP), as well as determine the acetylcholinesterase activity and the BDNF levels. Our results show that physical exercise and green tea are effective neuroprotective antioxidant strategies in a MD model. They also demonstrate that environmental enrichment is capable to reverse the deleterious effects of MD by increasing BDNF levels. These results reveal the possibility of using these interventions as a neuroprotection strategy.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-27T15:14:42Z No. of bitstreams: 1 MARIZA LIMA.pdf: 1903438 bytes, checksum: 3dd92f0052ecc6a9e39c2d2a9519ff7d (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-27T15:15:30Z (GMT) No. of bitstreams: 1 MARIZA LIMA.pdf: 1903438 bytes, checksum: 3dd92f0052ecc6a9e39c2d2a9519ff7d (MD5) / Made available in DSpace on 2018-09-27T15:15:30Z (GMT). No. of bitstreams: 1 MARIZA LIMA.pdf: 1903438 bytes, checksum: 3dd92f0052ecc6a9e39c2d2a9519ff7d (MD5) Previous issue date: 2017 / A Doença de Alzheimer (DA) é uma enfermidade incurável que causa perda das funções cognitivas (memória, orientação, atenção e linguagem). As lesões cerebrais são características dessa doença, sendo as principais alterações: as placas senis decorrentes do depósito de proteína beta-amiloide (βa) anormalmente produzida, e os emaranhados neurofibrilares. Atualmente, muitas abordagens são propostas para tratar ou prevenir a DA, mas os estudos geralmente usam protocolos que dificilmente permitem o estabelecimento da relação causa-efeito, pois envolvem mais de uma variável que poderia ter benefícios no cérebro com DA. O objetivo deste trabalho foi avaliar e isolar os efeitos neuroprotetores do enriquecimento ambiental, do exercício físico anaeróbio, e do enriquecimento social, em déficits de memória relacionados à neurotoxicidade induzida pela beta-amiloide (βa) em um modelo animal. Para isto, foram utilizados ratos Wistar submetidos às intervenções propostas por 8 semanas, e, logo após, à cirurgia estereotáxica para a injeção de βa no hipocampo. A memória foi avaliada pelos testes de reconhecimento de objetos e reconhecimento social, considerando memória de curta e de longa duração. O estado de oxidativo do hipocampo (níveis de espécies reativas de oxigênio, peroxidação lipídica e capacidade antioxidante total - ROS, TBARS e FRAP) e a atividade da enzima acetilcolinesterase (AChE) também foram verificados. Os dados mostram que a injeção de βa resultou em déficits de memória e danos oxidativos no hipocampo. O enriquecimento ambiental e o exercício físico 8 evitaram todos os déficits de memória e a peroxidação lipídica (TBARS) hipocampal induzida por βa. O enriquecimento social evitou apenas o déficit de memória de reconhecimento social induzido pela beta-amiloide e aumentou a capacidade antioxidante total (FRAP). / Alzheimer's Disease (AD) is an incurable disease that causes loss of cognitive functions (memory, orientation, attention, and language). Brain lesions are characteristic of this disease, in which main alterations being: senile plaques arisvel from the deposition of abnormally produced beta-amyloid protein (βa) and neurofibrillary tangles. Many approaches have been proposed to treat or prevent AD, but studies generally use protocols that becouse difficult to attribute a cause-effect relationship because they involve more than one variable that could be benefical in observed changes. The objective of this work was to evaluate and isolate the neuroprotective effects of environmental enrichment, anaerobic physical exercise, and social enrichment on memory deficits related to beta-amyloid neurotoxicity in an animal model. For this, Wistar rats were submitted to 8 weeks of intervention, and soon thereafter underwent stereotactic surgery for the injection of βa into the hippocampus. The memory was evaluated by object recognition and social recognition memory tests, considering short and long term memory. The oxidative state of the hippocampus (ROS, TBARS and FRAP) and acetylcholinesterase (AChE) activity are also verified. The data show that the injection of βa resulted in memory deficits and oxidative damage in the hippocampus. Environmental enrichment and exercise avoided all memory deficits and hippocampal lipid peroxidation (TBARS) induced by βa. Social enrichment avoided only the social 10 recognition memory deficit and avoided the total antioxidant capacity (FRAP) decrease induced by βa.

Respostas adaptativas ao estresse podem ser acompanhadas por alterações nos comportamentos emocionais, em particular relacionados com medo e ansiedade, bem como alterações na sensibilidade dolorosa. Ainda, tem sido investigado o papel do óxido nítrico em áreas encefálicas relacionadas ao comportamento defensivo. Embora várias evidências têm demonstrado que o enriquecimento ambiental promove melhora nos processos de memória, no aprendizado e em respostas nociceptivas, a relação entre o estresse crônico e as vantagens da utilização do enriquecimento ambiental ainda são pouco investigadas. O presente estudo teve como objetivo investigar se o enriquecimento ambiental promove alteração do comportamento emocional, da sensibilidade nociceptiva, bem como na imunorreatividade à nNOS no núcleo central da amígdala, na formação hipocampal e na região dorsolateral da substância cinzenta periaquedutal, em ratos submetidos ao estresse por isolamento social ou estresse crônico variado e mantidos em ambiente enriquecido ou sem enriquecimento. Ratos machos Wistar (~70g) foram divididos aleatoriamente em dois grandes grupos experimentais: Ambiente Padrão (Padrão) ou Ambiente Enriquecido (EE), mantidos por 38 dias. Cada grupo foi subdividido dependendo do tipo de estresse crônico: Controle (sem estresse), Isolamento Social (por 38 dias) e Estresse Crônico Variado (do dia 28 ao dia 37). Ao fim do tempo experimental (dia 38) os ratos foram avaliados quanto ao comportamento emocional pelos testes de labirinto em cruz elevado (LCE) e claro/escuro (TCE) e sensibilidade nociceptiva pelo teste da placa quente (a qual foi realizada em duas etapas, sendo a primeira medida no dia 0 e outra no dia 38). A eutanásia dos ratos ocorreu no dia 39, para coleta do encéfalo para análise da imunorreatividade à óxido nítrico sintase neuronal (nNOS). Levando-se em consideração o comportamento emocional e a sensibilidade nociceptiva, os diferentes tipos de estresse crônico diminuíram a porcentagem de tempo, a frequência de entrada e a exploração da extremidade dos braços abertos e na frequência de mergulho de cabeça no teste do LCE, apesar de não alterar a sensibilidade nociceptiva. Por outro lado, o enriquecimento ambiental aumentou a porcentagem de tempo, a frequência de entrada e a exploração da extremidade dos braços abertos no teste do LCE, apesar de não alterar a sensibilidade nociceptiva. Foi observado aumento da imunorreatividade à nNOS na formação hipocampal em diferentes tipos de estresse crônico. Em particular, na região de CA3 houve interação significante entre os fatores estresse por isolamento social e ambiente de manutenção. Deste modo, os resultados obtidos neste trabalho sugerem que a formação hipocampal desempenha importante função no efeito ansiogênico exercido pelos diferentes tipos de estressores crônicos (aqui representados pelo isolamento social e pelo estresse crônico variado) provavelmente pela ativação do sistema nitrérgico e sugere-se que o enriquecimento possa prevenir o comportamento do tipo ansioso. / Adaptive responses to stress may be accompanied by changes in emotional behaviors, in particular related to fear and anxiety, as well as changes in pain sensitivity. Furthermore, the role of nitric oxide in brain areas related to defensive behavior has been investigated. Although several evidences have shown that environmental enrichment improves memory processes, learning and nociceptive responses, the relationship between chronic stress and the advantages of using environmental enrichment is still poorly investigated. The present study aimed to investigate whether environmental enrichment promotes alteration of the emotional behavior, nociceptive sensitivity, as well as immunoreactivity to neuronal nitric oxide synthase (nNOS) in the central nucleus of the amygdala, hippocampal formation and dorsolateral periaqueductal gray matter in rats submitted to social isolation stress or chronic unpredictable stress and reared in enriched environment or standard environment. Male Wistar rats (~ 70g) were randomly divided into two major experimental groups: Standard Environment (Standard) or Enriched Environment (EE), maintained for 38 days. Each group was subdivided according to the type of chronic stress: Control (without stress), Social Isolation (for 38 days) and Chronic Unpredictable Stress (from day 28 to day 37). At the end of the experimental time (day 38), the rats were evaluated for emotional behavior by elevated plus maze (EPM) and light/dark box (LDBT) tests and nociceptive sensitivity by the hot plate test (which was performed in two steps , the first being measured on day 0 and the other on day 38). Euthanasia of rats occurred on day 39, to collect the brain for nNOS immunoreactivity analysis. Taking into account emotional behavior and nociceptive sensitivity, the different types of chronic stress decreased the percentage of time, the frequency of entry of the open arms, end-arm exploration and the head dipping frequency in the EPM, despite of not altering the nociceptive sensitivity. On the other hand, environmental enrichment increased the percentage of time, the frequency of entry of the open arms and the end arm-exploration in the EPM test, although it did not alter the nociceptive sensitivity. Increased immunoreactivity to nNOS in hippocampal formation was observed in different types of chronic stress. In particular, in the CA3 region there was a significant interaction between stress factors due to social isolation and maintenance environment. Thus, the results obtained in this study suggest that hippocampal formation plays an important role in the anxiogenic effect exerted by the different types of chronic stressors (represented here by social isolation and by chronic chronic stress) probably due to the activation of the nitrergic system and it is suggested that environmental enrichment can prevent of anxiety-like behavior.

O Brasil possui grande diversidade de felinos selvagens e a maioria destes animais encontra-se ameaçada de extinção. A reprodução em cativeiro é ferramenta essencial para a conservação de espécies como felinos e, em geral, está diretamente relacionada ao bem-estar animal. O presente projeto objetivou o estudo do comportamento em cativeiro da jaguatirica (Leopardus pardalis), enfocando possíveis comportamentos anormais indicativos de condições ambientais sub-ótimas, e o teste de dois protocolos de enriquecimento ambiental (físico e alimentar), visando um melhor entendimento das necessidades desta espécie em cativeiro e a proposição de técnicas de manejo mais adequadas. Para tanto analisamos parâmetros comportamentais (método de varredura) e endócrinos (metabólitos fecais de corticosterona) de 12 indivíduos adultos e cativos na Associação Mata Ciliar, Jundiaí/SP. Com a análise conjunta dos dados de todos os indivíduos não foi possível sustentar a hipótese de influência do tratamento sobre o bem-estar, mas os resultados apontam para influências sazonais sob o comportamento dos animais (temperatura e fotoperíodo) e para um possível efeito danoso da remoção/interrupção do tratamento sobre o bem-estar. A análise individual também apontou, em alguns casos, para este efeito maléfico da remoção do tratamento e para resultados positivos quando se aplicam técnicas de enriquecimento ambiental, como redução da freqüência de comportamentos anormais, aumento do comportamento social não-agonista e redução da concentração de metabólitos de glicocorticóides. Foi encontrada ainda correlação positiva entre a concentração de metabólitos de corticosterona e comportamentos anormais. Dada a importância prática desta linha de pesquisa e a escassez de trabalhos com pequenos felinos brasileiros em cativeiro, apresentamos ainda algumas sugestões metodológicas para futuros experimentos. / Brazil exhibits a large variety of wild cat species, most of which under the threat of extinction. Reproduction in captivity is an essential tool for the conservation of these species, and it is directly linked to animal welfare. This project aimed the study of the behavior of the ocelot (a small-sized American wild cat; Leopardus pardalis under captivity, looking for potential abnormal behavior indicative of sub-optimal environmental conditions, and the testing of two environmental enrichment procedures (physical and alimentary) in search of a better understanding of this species\' needs in captivity and of better management techniques. For that, we analyzed behavioral (scan sampling) and endocrinal data (fecal corticosterone metabolites) from 12 adult captive individuais in the facilities of the Associação Mata Ciliar (Jundiaí, SP, Brazil). The analysis of data for the whole sample did not support the hypothesis predicting an influence of the environment enrichment procedures on the animals\' welfare, but pointed to seasonal influences on behavior, and to a possible harmful effect of the removal/interruption of the treatment on the welfare. The individual data analysis also pointed, in some cases, to a harmful effect of treatment removal, as well as to some positive results of the application of the environmental enrichment procedures, such as the reduction on the frequencies of abnormal behavior, a rise in non-agonist social behavior, and a reduction in the concentration levels of corticosteroid metabolites. We also found a positive correlation between concentration levels of corticosterone metabolites and abnormal behavior. Finally, given the practical relevance of this line of research and the lack of studies on small cats under captivity, we formulate some methodological suggestions for future research.

O Brasil possui grande diversidade de felinos selvagens e a maioria destes animais encontra-se ameaçada de extinção. A reprodução em cativeiro é ferramenta essencial para a conservação de espécies como felinos e, em geral, está diretamente relacionada ao bem-estar animal. O presente projeto objetivou o estudo do comportamento em cativeiro da jaguatirica (Leopardus pardalis), enfocando possíveis comportamentos anormais indicativos de condições ambientais sub-ótimas, e o teste de dois protocolos de enriquecimento ambiental (físico e alimentar), visando um melhor entendimento das necessidades desta espécie em cativeiro e a proposição de técnicas de manejo mais adequadas. Para tanto analisamos parâmetros comportamentais (método de varredura) e endócrinos (metabólitos fecais de corticosterona) de 12 indivíduos adultos e cativos na Associação Mata Ciliar, Jundiaí/SP. Com a análise conjunta dos dados de todos os indivíduos não foi possível sustentar a hipótese de influência do tratamento sobre o bem-estar, mas os resultados apontam para influências sazonais sob o comportamento dos animais (temperatura e fotoperíodo) e para um possível efeito danoso da remoção/interrupção do tratamento sobre o bem-estar. A análise individual também apontou, em alguns casos, para este efeito maléfico da remoção do tratamento e para resultados positivos quando se aplicam técnicas de enriquecimento ambiental, como redução da freqüência de comportamentos anormais, aumento do comportamento social não-agonista e redução da concentração de metabólitos de glicocorticóides. Foi encontrada ainda correlação positiva entre a concentração de metabólitos de corticosterona e comportamentos anormais. Dada a importância prática desta linha de pesquisa e a escassez de trabalhos com pequenos felinos brasileiros em cativeiro, apresentamos ainda algumas sugestões metodológicas para futuros experimentos. / Brazil exhibits a large variety of wild cat species, most of which under the threat of extinction. Reproduction in captivity is an essential tool for the conservation of these species, and it is directly linked to animal welfare. This project aimed the study of the behavior of the ocelot (a small-sized American wild cat; Leopardus pardalis under captivity, looking for potential abnormal behavior indicative of sub-optimal environmental conditions, and the testing of two environmental enrichment procedures (physical and alimentary) in search of a better understanding of this species\' needs in captivity and of better management techniques. For that, we analyzed behavioral (scan sampling) and endocrinal data (fecal corticosterone metabolites) from 12 adult captive individuais in the facilities of the Associação Mata Ciliar (Jundiaí, SP, Brazil). The analysis of data for the whole sample did not support the hypothesis predicting an influence of the environment enrichment procedures on the animals\' welfare, but pointed to seasonal influences on behavior, and to a possible harmful effect of the removal/interruption of the treatment on the welfare. The individual data analysis also pointed, in some cases, to a harmful effect of treatment removal, as well as to some positive results of the application of the environmental enrichment procedures, such as the reduction on the frequencies of abnormal behavior, a rise in non-agonist social behavior, and a reduction in the concentration levels of corticosteroid metabolites. We also found a positive correlation between concentration levels of corticosterone metabolites and abnormal behavior. Finally, given the practical relevance of this line of research and the lack of studies on small cats under captivity, we formulate some methodological suggestions for future research.

Adolescence is a critical developmental period in which the brain emerges from an immature state to adulthood. This process of brain development is associated to greater cognitive capacity but also to altered emotional behaviour, such as anxiety and depressive symptoms; as well as increased sensation-seeking and risk taking behaviour. The proper development of brain and behaviour into adulthood can be negatively affected by external factors such as drug abuse and environmental conditions. This work consists firstly on, studying the impact of binge ethanol, 3, 4-Methylenedioxymethamphetamine (MDMA) and its combination in adolescent mice. Secondly, study the consequences of early-life stressful experiences (social isolation) into adulthood. Main results obtained from the first objective are that the combination of binge ethanol and MDMA induces emotional-like alterations. These alterations can be prevented by antidepressant treatment. In addition, MDMA induces memory impairments that may be associated to oxidative damage to specific proteins in the hippocampus. Neuroinflammation is also present after MDMA treatment, but not after binge ethanol treatment, in mice striatum. Metabolomic studies indicate that brain metabolism is altered after binge ethanol, MDMA or its combination. Even though these are only preliminary results, these alterations might be due to an imbalance in tryptophan metabolism. Regarding the second objective, our findings indicate that social isolation during adolescence induces an altered response to novel and stressful situations. These alterations are probably due to altered HPA axis activity. / L'adolescència és un període crític en el desenvolupament de l’individu en el qual el cervell va d’un estat immadur a l’edat adulta. Aquest procés va acompanyat d’una elevada capacitat cognitiva però també de freqüents alteracions de tipus emocional, com l’ansietat o els símptomes depressius, així com la cerca de sensacions de risc. Un bon desenvolupament del cervell i del comportament es pot veure negativament afectat per factors externs com són l’abús de drogues i les condicions ambientals desfavorables. Aquest projecte consisteix en primer lloc, a estudiar l'impacte de l’alcohol en excés, la 3, 4-Metilendioximetamfetamina (MDMA) i la seva combinació en ratolins adolescents. En segon lloc, estudiar les conseqüències en l’edat adulta d’experiències estressants durant l’adolescència. Els principals resultats obtinguts referents al primer objectiu són que la combinació d'alcohol en excés i MDMA provoca alteracions de tipus emocional. Aquestes alteracions poden ser previngudes pel tractament amb antidepressius. A més, la MDMA indueix un deteriorament de la memòria que pot estar associada amb el dany oxidatiu a proteïnes específiques de l'hipocamp. També s’ha observat una resposta neuroinflamatòria en el cos estriat dels ratolins després del tractament amb MDMA, però no després del tractament amb etanol en excés. Finalment, estudis de metabolòmica indiquen que el metabolisme cerebral es veu alterat després de l’alcohol en excés, la MDMA o la seva combinació. Tot i que només són resultats preliminars, aquestes alteracions poden ser conseqüència d'un desequilibri en el metabolisme del triptòfan. Referent al segon objectiu, els nostres resultats indiquen que l'aïllament social durant l’adolescència indueix una resposta alterada a situacions novelles i estressants. Aquestes respostes anormals són probablement conseqüència d’alteracions en l’activitat de l’eix HPA.

Introduction: Chez les mammifères, la naissance de nouveaux neurones se poursuit à l’âge adulte dans deux régions du cerveau: 1) l’hippocampe et 2) la zone sous-ventriculaire du prosencéphale. La neurogenèse adulte n’est pas un processus stable et peut être affectée par divers facteurs tels que l’âge et la maladie. De plus, les modifications de la neurogenèse peuvent être à l’origine des maladies de sorte que la régulation ainsi que le rétablissement de la neurogenèse adulte doivent être considérés comme d’importants objectifs thérapeutiques. Chez la souris saine ou malade, la neurogenèse hippocampale peut être fortement régulée par l’enrichissement environnemental ainsi que par l’activité physique. Cependant, lors même que l’activité physique et l’enrichissement environnemental pourraient contribuer au traitement de certaines maladies, très peu d’études porte sur les mécanismes moléculaires et physiologiques responsables des changements qui sont en lien avec ces stimuli. Objectifs et hypothèses: Les principaux objectifs de cette étude sont de caractériser les effets de stimuli externes sur la neurogenèse et, par le fait même, d’élucider les mécanismes sous-jacents aux changements observés. En utilisant le modèle d’activité physique volontaire sur roue, cette étude teste les deux hypothèses suivantes: tout d’abord 1) qu’une période prolongée d’activité physique peut influencer la neurogenèse adulte dans le prosencéphale et l’hippocampe, et 2) que l’activité volontaire sur roue peut favoriser la neurogenèse à travers des stimuli dépendants ou indépendants de la course. Méthodes: Afin de valider la première hypothèse, nous avons utilisé un paradigme incluant une activité physique volontaire prolongée sur une durée de six semaines, ainsi que des analyses immunohistochimiques permettant de caractériser l’activité de précurseurs neuronaux dans la zone sous-ventriculaire et l’hippocampe. Ensuite, pour valider la seconde hypothèse, nous avons utlisé une version modifiée du paradigme ci-dessous, en plaçant les animaux (souris) soit dans des cages traditionnelles, soit dans des cages munies d’une roue bloquée soit dans des cages munies d’une roue fonctionnelle. Résultats: En accord avec la première hypothèse, l’activité physique prolongée volontaire a augmenté la prolifération des précurseurs neuronaux ainsi que la neurogenèse dans le gyrus dentelé de l’hippocampe comparativement aux animaux témoins, confirmant les résultats d’études antérieures. Par ailleurs, dans ce paradigme, nous avons aussi observé de la prolifération acrue au sein de la zone sous-ventriculaire du prosencéphale. De plus, en accord avec la seconde hypothèse, les souris placées dans une cage à roue bloquée ont montré une augmentation de la prolifération des précurseurs neuronaux dans l’hippocampe comparable à celle observée chez les souris ayant accès à une roue fonctionnelle (coureurs). Cependant, seuls les animaux coureurs ont présenté une augmentation de la neurogenèse hippocampale. Conclusions: Ces résultats nous ont permis de tirer deux conclusions nouvelles concernant les effets de l’activité physique (course) sur la neurogenèse. Premièrement, en plus de la prolifération et de la neurogenèse dans le gyrus dentelé de l’hippocampe, la prolifération dans la zone sous-ventriculaire du prosencéphale peut être augmentée par l’activité physique sur roue. Deuxièmement, l’environnement dans lequel l’activité physique a lieu contient différents stimuli qui peuvent influencer certains aspects de la neurogenèse hippocampale en l’absence d’activité physique sur roue (course). / Introduction: In mammals, new neurons continue to be produced throughout the adulthood in two brain regions: 1) the hippocampus and 2) the forebrain subventricular zone. Adult neurogenesis is not a stable process, and changes in response to diverse factors such as age and pathology. Furthermore, because changes in neurogenesis may in fact underlie pathogenesis, regulating or restoring neurogenesis is seen as an important therapeutic objective. In healthy and diseased mice, hippocampal neurogenesis can be robustly regulated by environmental enrichment. However, while physical activity and environmental enrichment are potentially important in the treatment of some pathologies, comparatively little is known about the molecular and physiological mechanisms underlying activity/environment-dependent changes in neurogenesis. Objectives and hypotheses: The primary objectives of this study are to characterize the neurogenesis-mediating effects of external stimuli and, in doing so, to elucidate the mechanisms that underlie observed changes. Using voluntary wheel running as a model, this study addresses two hypotheses: 1) that extended periods of physical activity can influence adult neurogenesis in the forebrain and the hippocampus and 2) that voluntary wheel running mediates neurogenesis through both running-dependent and running-independent stimuli. Methods: To address the first hypothesis, we used a prolonged six-week voluntary paradigm and immunohistochemical analyses to characterize neural precursor activity in the subventricular zone and hippocampus. To address the second hypothesis, we used a modified version of the above paradigm, where an additional group of mice were housed in cages with a locked running wheel. Results: With respect to the first hypothesis, prolonged voluntary wheel running was found to increase neural precursor proliferation and neurogenesis in the hippocampal dentate gyrus relative to control animals, confirming the results of previous studies. More importantly, in this paradigm, proliferation in the forebrain subventricular zone was also found to be increased. In keeping with the second hypothesis, mice that were housed in locked-running wheel cages showed an increase in hippocampal neural precursor proliferation comparable to that of running animals. However, only running animals displayed increased hippocampal neurogenesis. Conclusions: These results allow us to draw two novel conclusions regarding the effects of running on neurogenesis. First, proliferation in the forebrain subventricular zone, in addition to proliferation and neurogenesis in the hippocampus, is subject to regulation by wheel-running. Second, the wheel-running environment contains diverse stimuli which can influence some aspects of hippocampal neurogenesis in the absence of wheel running.

Eating disorders are serious psychological disorders associated with debilitating lifestyle, multiple health problems and high rates of suicidality and mortality. Despite extensive research, the aetiology of eating disorders still remains unclear. Amongst the identified risk factors for eating disorders, stress has been frequently studied. The purpose of the present study was to explore the possibility that tail-pinch administered to rats could provide an animal model of stress-induced eating disturbances in humans, and whether environmental enrichment might ameliorate the effects of stress. In Experiment 1, we compared eating behaviours of rats that were reared in either enriched or standard environments and later exposed to tail-pinch and allowed to eat when food deprived. The study showed that a single exposure to tail-pinch induced eating disturbances in most of the rats. When rats were not food deprived, but were conditioned to eating when placed in test chamber, tail-pinch suppressed eating in all rats, but significantly more for rats reared under standard than in enriched conditions. Experiment 2 used a between-subjects design in which rats were reared in either a standard or enriched environment, and were either exposed to tail-pinch or not exposed during sessions in which they were not food deprived and allowed to eat. Tail-pinch suppressed the food intake of rats reared in enriched but not standard environments. Although this finding appeared to contradict results of Experiment 1, analysis of body weight revealed that exposure to tail pinch suppressed increases in weight gain across sessions more for rats reared in standard than enriched environments. The suppression of food intake during test sessions for enriched but not standard rats exposed to tail-pinch was attributed to differences in contextual conditioning and discrimination of the test chamber from home cages. Overall, results of the present study suggest that rats reared in enriched environments were more resilient to the effects of tail-pinch as a stressor. Implications of these findings for the understanding of human eating disorders are discussed.