Banca de QUALIFICAÇÃO: JULIANA ALVES BRANDAO MEDEIROS DE SOUSA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : JULIANA ALVES BRANDAO MEDEIROS DE SOUSA
DATA : 26/06/2018
HORA: 14:00
LOCAL: INSTITUTO DO CEREBRO
TÍTULO:

Genetic inheritance of social behavior and neural circuitry of the prefrontal cortex in an animal model of autism

PALAVRAS-CHAVES:

autism, VPA, social behavior, parvalbumin, epigenetic inherance

PÁGINAS: 113
GRANDE ÁREA: Ciências Biológicas
ÁREA: Fisiologia
RESUMO:

Autism comprises a heterogeneous group of disorders characterized by sensory, motor, language and mainly social deficits perceived in early childhood. Genetic factors, as well as environmental factors, are strongly involved in the predisposition to autism. Studies in animal models suggest that alterations in neural development may modify the pattern of differentiation and neuronal maturation, generating a hyper-excitable brain circuitry that could explain the characteristic symptomatology of autism. The animal model induced by administration of VPA in pregnant rats was previously characterized by our group. We have shown that F1 animals born to females exposed to VPA have "autistic" behaviors, such as hyperlocomotion, prolonged stereotypy, and reduced social interaction. Histologically, we detected a reduction in the number of parvalbumin (PV) + interneurons in the medial prefrontal cortex (mPFC) of F1 animals. In the present work, we investigated the possibility of herdability transmission of changes caused by VPA in F1 animals. For this, we analyze the behavior and the histology of the CPFm of animals generated by F1 animals. These animals, hereafter referred as F2, were not directly exposed to VPA during gestation and therefore, behavioral and histological changes may suggest the genetic heritability of VPA-induced traits in F1. We observed that the F2 generation presents absence of hyperlocomotion followed by reduction in the stereotyped and exploratory movement. On the other hand, F2 animals presented social deficit, althought in a milder form than F1 animals. On the other hand, histological analysis reveals an increase in the number of PV + neurons in the mPFC, suggesting that changes in excitation / inhibition levels occur in both F1 and F2 animals. Cross-fostering experiments corroborate the interpretation that the changes observed in F2 animals have a genetic basis. F2 animals cared for by the mother (F1) or naïve females have low levels of sociability. Surprisingly, this effect was even more intense in group F2 cared for by foster mothers, demonstrating that caring for these females was not only insufficient to reverse the low levels of social interaction presented by F2 animals, but also aggravated this social deficit in these animals. The data presented indicate that prenatal exposure to VPA induces genetic changes in rats that can be transmitted to their offspring. This model may contribute in the future to the identification of genetic signatures associated with the behavioral and histological changes observed in autism

MEMBROS DA BANCA:
Externo à Instituição - CECILIA HEDIN PEREIRA - UFRJ
Presidente - 1674643 - MARCOS ROMUALDO COSTA
Interno - 1698305 - RODRIGO NEVES ROMCY PEREIRA
Interno - 2183828 - TARCISO ANDRE FERREIRA VELHO