Banca de DEFESA: JULIANA ALVES BRANDAO MEDEIROS DE SOUSA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : JULIANA ALVES BRANDAO MEDEIROS DE SOUSA
DATA : 10/08/2018
HORA: 15:00
LOCAL: INSTITUTO DO CEREBRO
TÍTULO:
PALAVRAS-CHAVES:

autism, VPA, social behavior, parvalbumin, epigenetic inheritance.

PÁGINAS: 140
GRANDE ÁREA: Ciências Biológicas
ÁREA: Fisiologia
RESUMO:

Autism comprises a heterogeneous group of disorders characterized by sensory, motor, language and mainly social deficits perceived early in childhood. Genetic and epigenetic factors, as well as environmental factors, are strongly involved in the predisposition to autism. Studies in animal models of the disease suggest that these same factors can alter the development of the central nervous system, modifying patterns of differentiation and neuronal maturation and generating a dysfunctional brain circuitry. Therefore, identifying the neural changes in the developing brain can provide clues about the causes and possible treatments of autism. Our group previously characterized the animal model induced by administration of VPA in pregnant rats. We demonstrated that VPA-exposed animals during pregnancy (F1_VPA) exhibit "autistic" behaviors in postnatal life, such as hyper locomotion, 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 these animals compared to controls. Considering the effects of VPA on chromatin structure and DNA methylation, we hypothesized that behavioral and histological changes observed in F1_VPA animals would be transmissible for the next generation, independent of new VPA exposures. In this work, we analyzed the behavior and histology of mPFC in F1_VPA progeny, hereafter referred to as F2. We observed that these animals present a significant reduction in social interaction and in the frequency of exploratory surveys when compared to control animals. This reduction in social preference, however, was intermediate between that presented by control animals and F1_VPAanimals, with the latter showing the most severe deficit in social behavior. On the other hand, we observe neither hyper locomotion, nor alterations in the exploratory ambulation or stereotyped behaviors in F2 animals when compared to the controls. Locomotion, exploration and stereotypies had their profiles normalized with respect to F1_VPA animals. In order to test whether behavioral impairments in F2 stemmed from differences in parental care of VPA mothers and control mothers on their offspring, we performed cross-fostering experiments. We observed that F2 animals cared for by control mothers presented low rates of sociability when compared to control animals cared for by control mothers, which corroborates the interpretation that the observed changes in F2 animals are epigenetically inherited. The histological evaluation of cortical tissue revealed an increase in the number of PV+ neurons in the mPFC in F2 animals, suggesting an excitatory/inhibitory imbalance in the fronto-cortical circuitry, also observed in F1_VPA animals, but in the opposite direction. Therefore, the data presented indicate that prenatal exposure to VPA induces epigenetic 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
Externo à Instituição - CLEITON LOPES AGUIAR - UFMG
Interno - 2394627 - EDUARDO BOUTH SEQUERRA
Interno - 1976236 - EMELIE KATARINA SVAHN LEAO
Presidente - 1674643 - MARCOS ROMUALDO COSTA
Interno - 1698305 - RODRIGO NEVES ROMCY PEREIRA