Efeitos do canabidiol e possível dimorfismos sexuais em um modelo animal de autismo
Data
2022-11-25
Autores
Teodoro, Lucas 
Orientadores
Abílio, Vanessa Costhek
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
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Resumo
O transtorno do espectro autista (TEA) é o transtorno do neurodesenvolvimento que mais cresce no mundo. Caracteriza-se por déficits na comunicação e interação social, bem como pelo aparecimento de comportamentos repetitivos e estereotipados. A prevalência é maior em homens do que em mulheres, mas as mulheres escondem melhor seus defeitos, o que se reflete nas diferentes taxas de prevalência entre os sexos e na idade mais avançada do diagnóstico na população feminina. As medidas farmacológicas atualmente têm baixa eficácia, e algumas evidências clínicas e pré-clínicas sugerem o canabidiol (CBD) como uma possibilidade terapêutica. A exposição gestacional ao ácido valpróico (VPA) é um fator de risco para o desenvolvimento do TEA e um modelo animal amplamente utilizado para avaliar alterações comportamentais associadas ao transtorno. Assim, os objetivos deste estudo foram: 1) avaliar em diferentes idades possíveis dimorfismos sexuais sobre as alterações comportamentais observadas no modelo animal de autismo induzido por VPA (atividade motora, sociabilidade, processamento sensório-motor e comportamento repetitivo); e 2) avaliar possíveis efeitos benéficos do CBD sobre essas alterações comportamentais no modelo animal de autismo induzido por VPA. Para isso, foram realizados dois experimentos. No Experimento 1, foi realizada uma bateria de testes comportamentais em períodos diferentes do desenvolvimento (DPN 30-32, DPN 45-47 e DPN 60-62). A bateria de testes comportamentais consistiu no teste de interação social, teste de marble burying e o teste de inibição pré-pulso (PPI). No experimento 2, os animais foram tratados cronicamente com CBD (0,5 mg/kg) durante 30 dias pós-desmame (DPN 22-51) e uma série de testes comportamentais foram realizados em dois períodos de desenvolvimento: o período peripuberal (DPN 30-34) e no início da fase adulta (DPN 60-65). A bateria de testes comportamentais consistiu em dois dias campo aberto, um teste de interação social, um teste de preferência social, um teste de marble burying e um teste de PPI. Observamos que a administração de VPA durante a gravidez induz mudanças comportamentais que podem diferir entre sexos e idades. O tratamento com CBD mostrou evidências de um potencial efeito benéfico no déficit social induzido no modelo.
Autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder in the world. It is characterized by deficits in communication and social interaction, as well as by the appearance of repetitive and stereotyped behaviors. The prevalence is higher in men than in women, but women hide their defects better, which is reflected in the different prevalence rates between the sexes and in the older age of diagnosis in the female population. Pharmacological measures currently have low efficacy, and some clinical and preclinical evidence suggests cannabidiol (CBD) as a therapeutic possibility. Gestational exposure to valproic acid (VPA) is a risk factor for the development of ASD and a widely used animal model to assess behavioral changes associated with the disorder. Thus, the objectives of this study were: 1) to evaluate possible sexual dimorphisms at different ages on the behavioral changes observed in the animal model of autism induced by VPA (motor activity, sociability, sensorimotor processing, and repetitive behavior); and 2) to evaluate possible beneficial effects of CBD on these behavioral changes in the animal model of autism induced by VPA. For this, two experiments were carried out. In Experiment 1, a battery of behavioral tests was carried out at different periods of development (PND 30-32, DPN 45-47 and DPN 60-62). The battery of behavioral tests consisted of the social interaction test, the marble burying test and the prepulse inhibition test (PPI). In experiment 2, the animals were chronically treated with CBD (0.5 mg/kg) for 30 days post-weaning (PDN 22-51) and a series of behavioral tests were performed in two developmental periods: the peripubertal period (PDN 30-34) and early adulthood (PND 60-65). The battery of behavioral tests consisted of two days in the open field, a social interaction test, a social preference test, a marble burying test, and a PPI test. We observed that administration of VPA during pregnancy induces behavioral changes that may differ between sexes and ages. CBD treatment showed evidence of a potential beneficial effect on the social deficit induced in the model.
Autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder in the world. It is characterized by deficits in communication and social interaction, as well as by the appearance of repetitive and stereotyped behaviors. The prevalence is higher in men than in women, but women hide their defects better, which is reflected in the different prevalence rates between the sexes and in the older age of diagnosis in the female population. Pharmacological measures currently have low efficacy, and some clinical and preclinical evidence suggests cannabidiol (CBD) as a therapeutic possibility. Gestational exposure to valproic acid (VPA) is a risk factor for the development of ASD and a widely used animal model to assess behavioral changes associated with the disorder. Thus, the objectives of this study were: 1) to evaluate possible sexual dimorphisms at different ages on the behavioral changes observed in the animal model of autism induced by VPA (motor activity, sociability, sensorimotor processing, and repetitive behavior); and 2) to evaluate possible beneficial effects of CBD on these behavioral changes in the animal model of autism induced by VPA. For this, two experiments were carried out. In Experiment 1, a battery of behavioral tests was carried out at different periods of development (PND 30-32, DPN 45-47 and DPN 60-62). The battery of behavioral tests consisted of the social interaction test, the marble burying test and the prepulse inhibition test (PPI). In experiment 2, the animals were chronically treated with CBD (0.5 mg/kg) for 30 days post-weaning (PDN 22-51) and a series of behavioral tests were performed in two developmental periods: the peripubertal period (PDN 30-34) and early adulthood (PND 60-65). The battery of behavioral tests consisted of two days in the open field, a social interaction test, a social preference test, a marble burying test, and a PPI test. We observed that administration of VPA during pregnancy induces behavioral changes that may differ between sexes and ages. CBD treatment showed evidence of a potential beneficial effect on the social deficit induced in the model.
Descrição
Citação
TEODORO, L. Efeitos do canabidiol e possível dimorfismos sexuais em um modelo animal de autismo. São Paulo, 2022. 229 f. Dissertação (Mestrado em Farmacologia) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). São Paulo, 2022.