Efeitos comportamentais da ovariectomia em um modelo animal neurodesenvolvimental de esquizofrenia
Data
2024-10-18
Autores
Souza, Jaqueline Castelani de 
Orientadores
Abílio, Vanessa Costhek
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A esquizofrenia, um transtorno psiquiátrico do neurodesenvolvimento, tem um impacto significativo na vida dos pacientes e de seus familiares. Apesar da prevalência semelhante entre homens e mulheres, a condição apresenta características dimórficas em relação ao sexo, manifestando-se de maneira distinta em termos de idade de início, tipo e gravidade dos sintomas. Essas variações sugerem uma possível influência dos hormônios sexuais na fisiopatologia da esquizofrenia, com destaque para o estradiol. É digno de nota o aparecimento tardio e o agravamento dos sintomas em mulheres durante a peri- e pós-menopausa, um período marcado por uma queda acentuada nos níveis plasmáticos de estradiol. Diante desse cenário, o presente estudo teve como objetivo geral caracterizar o perfil comportamental de ratas adultas submetidas à ovariectomia e tratadas com um antagonista não-competitivo do receptor NMDA (MK-801) durante o período neonatal. No primeiro experimento, as fêmeas foram submetidas a tratamento diário com 0,5 mg/kg de MK-801 do DPN 05 ao DPN 12, a ovariectomia (OVX) no DPN 90 e, posteriormente, a uma série de comportamentos do DPN 120 ao DPN 140. Já no Experimento 2, as ratas receberam tratamento com 0,5 mg/kg/dia de MK-801 entre o DPN 07 e o DPN 20 e foram submetidas à cirurgia de OVX no DPN 90, passando pelas tarefas comportamentais em três momentos: entre o DPN 45-49, entre o DPN 85-89, e entre DPN 135-139. Os resultados comportamentais do Experimento 1 revelaram uma redução da atividade locomotora espontânea e induzida por psicoestimulante em animais tratados com MK-801 e OVX. Com relação ao comportamento social, foi observado alta preferência pela “zona social” em todos os grupos, especialmente nos animais OVX. O teste de PPI revelou um déficit de funcionamento do filtro sensório-motor especificamente em animais MK-801 + OVX. Por sua vez, o Experimento 2 revelou atraso da abertura vaginal de ratas tratadas com MK-801, além de aumento do perfil locomotor (DPN 136) e do número de rotações (DPN 45, 46, e 136) nos animais tratados com MK-801. Também foi observado déficit cognitivo no teste de alternação espontânea e elevada preferência social em todos os grupos do Experimento 2, mas sem qualquer prejuízo de PPI. Em resumo, os achados sugerem um possível efeito do estrógeno sobre os principais neurotransmissores associados à esquizofrenia. Essa conexão entre a regulação hormonal e os sintomas comportamentais destaca a importância da compreensão dos mecanismos neurobiológicos subjacentes à esquizofrenia, visando potenciais intervenções terapêuticas centradas nos hormônios sexuais.
Schizophrenia, a neurodevelopmental psychiatric disorder, has a significant impact on the lives of patients and their families. Despite the similar prevalence in men and women, the condition exhibits sex-dimorphic characteristics, manifesting differently in terms of age of onset, type, and severity of symptoms. These variations suggest a potential influence of sex hormones on the pathophysiology of schizophrenia, with particular emphasis on estradiol. Notably, the late onset and worsening of symptoms in women during peri- and post-menopause, a period marked by a sharp decline in plasma estradiol levels, are of great importance. In this context, the present study aimed to characterize the behavioral profile of adult female rats subjected to ovariectomy and treated with a non-competitive NMDA receptor antagonist (MK-801) during the neonatal period. In the first experiment, females were treated daily with 0.5 mg/kg of MK-801 from PND 05 to PND 12, underwent ovariectomy (OVX) at PND 90, and underwent a series of behavioral tests from PND 120 to PND 140. In Experiment 2, the rats received 0.5 mg/kg/day of MK-801 between PND 07 and PND 20, underwent OVX surgery at PND 90, and were subjected to behavioral tasks at three time points: between PND 45-49, PND 85-89, and PND 135-139. Behavioral results from Experiment 1 revealed a reduction in spontaneous and psychostimulant-induced locomotor activity in animals treated with MK-801 and OVX. Regarding social behavior, a high preference for the “social zone” was observed in all groups, especially in OVX animals. The PPI test revealed a deficit in sensorimotor gating function specifically in MK-801 + OVX animals. In contrast, Experiment 2 showed delayed vaginal opening in MK-801-treated rats, as well as increased locomotor activity (PND 136) and the number of rotations (PND 45, 46, and 136) in MK-801-treated animals. Cognitive deficits in the spontaneous alternation test and a high social preference in all groups of Experiment 2 were also observed, though without any PPI impairment. In summary, the findings suggest a possible effect of estrogen on the major neurotransmitters associated with schizophrenia. This connection between hormonal regulation and behavioral symptoms highlights the importance of understanding the neurobiological mechanisms underlying schizophrenia, aiming at potential therapeutic interventions focused on sex hormones.
Schizophrenia, a neurodevelopmental psychiatric disorder, has a significant impact on the lives of patients and their families. Despite the similar prevalence in men and women, the condition exhibits sex-dimorphic characteristics, manifesting differently in terms of age of onset, type, and severity of symptoms. These variations suggest a potential influence of sex hormones on the pathophysiology of schizophrenia, with particular emphasis on estradiol. Notably, the late onset and worsening of symptoms in women during peri- and post-menopause, a period marked by a sharp decline in plasma estradiol levels, are of great importance. In this context, the present study aimed to characterize the behavioral profile of adult female rats subjected to ovariectomy and treated with a non-competitive NMDA receptor antagonist (MK-801) during the neonatal period. In the first experiment, females were treated daily with 0.5 mg/kg of MK-801 from PND 05 to PND 12, underwent ovariectomy (OVX) at PND 90, and underwent a series of behavioral tests from PND 120 to PND 140. In Experiment 2, the rats received 0.5 mg/kg/day of MK-801 between PND 07 and PND 20, underwent OVX surgery at PND 90, and were subjected to behavioral tasks at three time points: between PND 45-49, PND 85-89, and PND 135-139. Behavioral results from Experiment 1 revealed a reduction in spontaneous and psychostimulant-induced locomotor activity in animals treated with MK-801 and OVX. Regarding social behavior, a high preference for the “social zone” was observed in all groups, especially in OVX animals. The PPI test revealed a deficit in sensorimotor gating function specifically in MK-801 + OVX animals. In contrast, Experiment 2 showed delayed vaginal opening in MK-801-treated rats, as well as increased locomotor activity (PND 136) and the number of rotations (PND 45, 46, and 136) in MK-801-treated animals. Cognitive deficits in the spontaneous alternation test and a high social preference in all groups of Experiment 2 were also observed, though without any PPI impairment. In summary, the findings suggest a possible effect of estrogen on the major neurotransmitters associated with schizophrenia. This connection between hormonal regulation and behavioral symptoms highlights the importance of understanding the neurobiological mechanisms underlying schizophrenia, aiming at potential therapeutic interventions focused on sex hormones.
Descrição
Citação
SOUZA, Jaqueline Castelani de. Efeitos comportamentais da ovariectomia em um modelo animal neurodesenvolvimental de esquizofrenia. 2024. 95 f. Dissertação (Mestrado em Farmacologia) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2024.