Estudo do envolvimento da neurotransmissão hipocampal nos mecanismo centrais das respostas comportamentais ao estresse crônico repetido
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Data
2022-12-16
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Universidade Estadual Paulista (Unesp)
Resumo
O estresse emocional causa um desequilíbrio fisiológico e psicológico no organismo.
A exposição prolongada ou repetida a ameaças reais ou potenciais inicia processos
adaptativos que visam minimizar o impacto do estresse sobre o organismo. Um importante
processo adaptativo é a habituação das respostas fisiológicas durante a exposição repetida
ao mesmo estímulo aversivo. Essas respostas fisiológicas são acompanhadas por
consequências emocionais, como o desenvolvimento de transtornos de ansiedade e
depressão, que parecem ser decorrentes de uma adaptação anormal do estresse. Entretanto,
apesar da importância da habituação das respostas ao estresse, os mecanismos
neurobiológicos e neuroquímicos envolvidos nesse processo ainda são pouco
compreendidos. Sendo assim, o objetivo do presente projeto foi avaliar o efeito da inativação
de neurônios hipocampais ventrais (através do método de inativação Daun02) ativados
previamente pelo estresse de restrição sobre as respostas comportamentais associadas ao
estresse crônico de restrição em ratas e ratos transgênicos c-Fos-lacZ. Os resultados
mostraram que o estresse agudo (veículo+RS) ou crônico (veículo+CRS) de restrição não
causou efeito relacionado à ansiedade nos testes do LCE e CA em ambos os sexos de
animais lacZ. No entanto, a microinjeção bilateral de Daun02 (inativação neuronal) no
hipocampo ventral (HV) promoveu um efeito do tipo ansiogênico nas ratas estressadas
cronicamente (Daun02+CRS) no teste do LCE. Além disso, os dados demonstraram que o
estresse crônico (veículo+CRS), mas não o estresse agudo (veículo+RS), causou um
aumento no tempo de “grooming” no ST em ambos os sexos dos animais lacZ. Já no FST, o
estresse agudo (veículo+RS) não causou nenhuma alteração nos parâmetros analisados
(nado, escalada e imobilidade) nos ratos lacZ. No entanto, o estresse agudo (veículo+RS)
causou um aumento do tempo de escalada e uma redução no tempo de imobilidade nas
fêmeas que foi revertido nos animais tratados com Daun02 (Daun02+RS). O estresse crônico
(veículo+CRS) causou um aumento no tempo de imobilidade nos ratos lacZ e uma redução o
tempo de imobilidade nas ratas lacZ e ambas as respostas foram revertidas nos animais
tratados com Daun02 (Daun02+CRS).
Emotional stress causes physiological and psychological imbalance in the body. Adaptive processes are triggered during repeated stress exposure that constitute important changes to minimizing stress impact on the body. An important adaptive process is physiological responses habituation during repeated exposure to the same aversive stimulus. These physiological responses are accompanied by emotional consequences such as development of anxiety and depression disorders, which appear to be due to an abnormal stress adaptation. However, even with proven importance of stress responses habituation, neurobiological and neurochemical mechanisms involved in this process are still poorly understood. Therefore, the aim of the present project was to evaluate the effect of ventral hippocampal neurons inactivation (through Daun02 inactivation method) previously activated by restraint stress on the behavioral responses associated with chronic restraint stress in female and male c-Fos-lacZ transgenic rats. The results showed that acute (vehicle+RS) or chronic (vehicle+CRS) restraint stress caused no anxiety-related effect observed in elevated pluz-maze and open filed tests in both gender of lacZ animals. However, bilateral microinjection of Daun02 (neuronal inactivation) into the ventral hippocampus (VH) promoted an anxiogenic-like effect observed in elevated pluz-maze in chronically stressed female rats (Daun02+CRS). Furthermore, the data demonstrated that chronic stress (vehicle+CRS), but not acute stress (vehicle+RS), caused an increase in grooming time in both genders of lacZ animals. In the FST, acute stress (vehicle+RS) caused no change in the analyzed parameters (swimming, climbing and immobility times) in lacZ male rats. However, acute stress (vehicle+RS) caused an increase in climbing time and a reduction in immobility time in female rats and both responses were reverted in Daun02-treated animals (Daun02+RS). Chronic stress (vehicle+CRS) caused an increase in immobility time in lacZ male rats and a reduction in immobility time in lacZ female rats and both responses were reverted in Daun02-treated animals (Daun02+CRS).
Emotional stress causes physiological and psychological imbalance in the body. Adaptive processes are triggered during repeated stress exposure that constitute important changes to minimizing stress impact on the body. An important adaptive process is physiological responses habituation during repeated exposure to the same aversive stimulus. These physiological responses are accompanied by emotional consequences such as development of anxiety and depression disorders, which appear to be due to an abnormal stress adaptation. However, even with proven importance of stress responses habituation, neurobiological and neurochemical mechanisms involved in this process are still poorly understood. Therefore, the aim of the present project was to evaluate the effect of ventral hippocampal neurons inactivation (through Daun02 inactivation method) previously activated by restraint stress on the behavioral responses associated with chronic restraint stress in female and male c-Fos-lacZ transgenic rats. The results showed that acute (vehicle+RS) or chronic (vehicle+CRS) restraint stress caused no anxiety-related effect observed in elevated pluz-maze and open filed tests in both gender of lacZ animals. However, bilateral microinjection of Daun02 (neuronal inactivation) into the ventral hippocampus (VH) promoted an anxiogenic-like effect observed in elevated pluz-maze in chronically stressed female rats (Daun02+CRS). Furthermore, the data demonstrated that chronic stress (vehicle+CRS), but not acute stress (vehicle+RS), caused an increase in grooming time in both genders of lacZ animals. In the FST, acute stress (vehicle+RS) caused no change in the analyzed parameters (swimming, climbing and immobility times) in lacZ male rats. However, acute stress (vehicle+RS) caused an increase in climbing time and a reduction in immobility time in female rats and both responses were reverted in Daun02-treated animals (Daun02+RS). Chronic stress (vehicle+CRS) caused an increase in immobility time in lacZ male rats and a reduction in immobility time in lacZ female rats and both responses were reverted in Daun02-treated animals (Daun02+CRS).
Descrição
Palavras-chave
Hipocampo, Respostas comportamentais, Estresse crônico de restrição, Ratos transgênicos c-Fos-lacZ, Behavioral responses, Chronic restraint stress, c-Fos-lacZ transgenic rat