Banca de DEFESA: DANIELA MARIA DE SOUSA MOURA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : DANIELA MARIA DE SOUSA MOURA
DATA : 30/08/2017
HORA: 14:00
LOCAL: INSTITUTO DO CEREBRO
TÍTULO:

Alterations in the cell lineage and neuronal organization in the adult dentate gyrus in two animal models of epilepsy

PALAVRAS-CHAVES:

Adult hippocampus; neurogenesis; astrogliogenesis; epilepsy; fate-specification; kainic acid; pilocarpine; GABAergic interneurons; granule cell dispersion; ectopic neurons; hilar basal dendrites, mouse.

PÁGINAS: 150
GRANDE ÁREA: Ciências Biológicas
ÁREA: Fisiologia
RESUMO:

The granular cells of the hippocampus are one of the few types of neurons generated in the central nervous system of adult mammals. The current model of neurogenesis in the adult hippocampus assumes that neural stem cells (NSCs) give rise to progenitors restricted to the generation of neurons or astrocytes. Environmental stimuli and pathological conditions can alter the lineage progression, modulating cell proliferation, differentiation, survival and synaptic integration of newly generated neurons. For example, mesial Temporal Lobe Epilepsy (mTLE), the most common form of epilepsy in adults, is associated with changes in the rate of adult hippocampal neurogenesis. In this work, we used two experimental mTLE models to evaluate the effects of an epileptogenic insult (i.e., status epilepticus, SE) on the cell lineage and neuronal maturation in the adult dentate gyrus. Using Dcx-CreERT2 / CAG-CAT-GFP animals, we fate mapped the fate of cells expressing the doublecortin gene (DCX) either before or after intrahippocampal injection of the convulsive agents kainic acid or pilocarpine. In this way, we could evaluate the effect of these drugs on DCX+ progenitors and immature neurons generated before or after treatment. In both models, we observed an increase of neurogenesis and changes in the positioning and morphology of granular cells, according to previous descriptions in the literature. Neuronal aberrations, such as ectopic localization and presence of basal dendrites, were observed both in cells generated before and after induction of ES, albeit at different frequencies. However, only in the hippocampus ipsilateral to the injection of kainic acid we observed granule cell dispersion and neuronal death in CA1 and CA3, although the paroxysmal epileptic activity occurred in both hippocampi. Surprisingly, the increase of neurogenesis in animals that received kainic acid was restricted to the contralateral hippocampus, whereas on the ipsilateral side a significant increase in astrocyte generation was observed within the DCX+ progenitor lineage. In addition, we also observed the presence of cells with NSC hallmarks, suggesting that DCX+ progenitors could regress to more primitive states in the adult hippocampal cell lineage. The increased astrogliogenesis on the ipsilateral side to the injection of kainic acid was associated with a degeneration of parvalbumin (PV)+ interneurons in the hippocampus, suggesting that GABAergic activity could be contributing to the rerouting of the DCX+ progenitor cell lineage. Taken together, our data indicate that the cell lineage in the dentate gyrus is neither unidirectional nor irreversible, and that the increased neuronal electrical activity induced by kainic acid and pilocarpine have different effects on cell differentiation and the fate of progenitors and neurons in that region. These results highlight the need to review the current model of adult hippocampal neurogenesis and also indicate that different animal models of epilepsy produce distinct cellular alterations in the adult hippocampus and could therefore represent different degrees / stages of the pathology.

MEMBROS DA BANCA:
Externo à Instituição - CECILIA HEDIN PEREIRA - UFRJ
Interno - 2069422 - DIEGO ANDRES LAPLAGNE
Interno - 1976236 - EMELIE KATARINA SVAHN LEAO
Externo à Instituição - GABRIEL MAISONNAVE ARISI - UNIFESP
Presidente - 1674643 - MARCOS ROMUALDO COSTA