Banca de DEFESA: CAROLINA ARAUJO SOUSA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : CAROLINA ARAUJO SOUSA
DATA : 31/08/2017
HORA: 09:00
LOCAL: INSTITUTO DO CEREBRO
TÍTULO:

POSTNATAL BRAIN MYELINATION IN A MODEL OF AUTISM INDUCED BY PRENATAL EXPOSURE TO VALPROIC ACID

 

PALAVRAS-CHAVES:

DEVELOPMENT OF NEURAL CIRCUITS, EXPERIMENTAL MODEL OF AUTISM, VALPROIC ACID, FRONTAL CORTEX, MYELIN, GENE EXPRESSION

PÁGINAS: 60
GRANDE ÁREA: Ciências Biológicas
ÁREA: Fisiologia
RESUMO:

The formation of brain circuits during neural development occurs through the interaction between timely regulated genetic and environmental signals, which influence multiple events such as neurogenesis, synaptogenesis, and myelination. In developmental disorders, such as autism spectrum disorders (ASD), deficits in these processes may lead to neural circuitry malformations and, in consequence, to social interaction deficits, restricted interests, and stereotyped movements, among others. Recently, we performed a transcriptome analysis of the frontal cortex of an animal model of autism induced by valproic acid (VPA) in utero in our lab. We observed that VPA animals at the postnatal age 15 (P15) show an increased expression of genes related to synaptic stability and a decrease in the expression of myelin-related genes, suggesting possible molecular mechanisms for the behavioral deficits previously observed in these animals. Therefore, the aim of this Master’s thesis was to further investigate the myelination pattern in the forebrain of VPA-treated rats at different postnatal ages (infant: P15 and adult: P60). For that, experimental and control groups were generated by injecting pregnant dams with 500 mg/Kg i.p. VPA or saline, respectively, on embryonic day 12.5 (E12.5). Analysis of myelin integrity was conducted by two different approaches: (1) gene expression analysis of myelin-related genes (Mobp, Plp1, Mag, and Klhl1) in dissected samples of the frontal cortex of P15 rats by quantitative real-time PCR; and (2) histological quantification of myelin distribution in five sub-regions of the frontal cortex and corpus callosum of P15 and P60 animals. Of all genes analyzed, we observed a significant decrease in Mobp and Mag expression in P15 VPA animals. Myelin analysis showed a significant reduction in myelin staining in the anterior cingulate cortex of VPA animals at P60, but no differences were observed at P15. In conclusion, infant VPA rats showed reduced expression of genes related to myelin assembly, without alterations in the lipid content of myelin in the areas analyzed. Adult animals, in contrast, showed a decrease in lipid content of myelin in the anterior cingulate cortex. Together, these results suggest that communication abnormalities in frontal circuits in this animal model of autism may occur initially due to alterations in myelin organization, leading to myelin reduction in adulthood.

MEMBROS DA BANCA:
Presidente - 1698305 - RODRIGO NEVES ROMCY PEREIRA
Interno - 2183828 - TARCISO ANDRE FERREIRA VELHO
Externo à Instituição - OLAGIDE WAGNER DE CASTRO - UFAL