Banca de QUALIFICAÇÃO: DANIELA MARIA DE SOUSA MOURA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : DANIELA MARIA DE SOUSA MOURA
DATA : 04/07/2017
HORA: 09:30
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; gliogenesis; epilepsy; fate-specification; kainic acid; pilocarpine; GABAergic interneurons; granule cell dispersion; ectopic neurons; hilar basal dendrites.

PÁGINAS: 125
GRANDE ÁREA: Ciências Biológicas
ÁREA: Fisiologia
RESUMO:

Mesial Temporal Lobe Epilepsy (mTLE) is the most common form of epilepsy in adults and its characteristics include structural and physiological alterations in the limbic system. Animal models of mTLE can be generated through the chemical induction of a sustained status epilepticus. Thus, animals treated with kainic acid (KA) or pilocarpine present remarkable cell death in hilus on the dentate gyrus and subfields of the Amon’s horn, as well as axonal reorganization and spontaneous and recurrent seizures. Acutely, the increase in neural excitability induced by both convulsive agents significantly enhances the proliferation of granular cells, one of the few regions with neurogenesis in the adult brain. Paradoxically, increased proliferation is unable to attenuate neuronal death associated with the epileptogenic insult. The current model of cell differentiation postulates that neural stem cells (NSCs) generate the neuronal progenitors, which become postmitotic in a unidirectional and irreversible way. Some NSCs may remain quiescent, and eventually, receive signals to proliferate and produce new neurons. Several environmental and genetic factors can interfere with this process, modulating the proliferation, survival, and integration of these newborn cells in the adult hippocampus. Understanding the tissue and cellular mechanisms associated with this phenomenon is of fundamental importance to comprehend the pathophysiology of the disease, besides helping in the development of new treatments. Thus, the present study evaluated the effects of two convulsive substances on the hippocampal neurogenesis of adult the mice. Using transgenic animals, we induced the expression of a fluorescent protein (GFP) in specific cell cohorts, which express the typical marker of young neurons (DCX), before or after intrahippocampal injection of KA or pilocarpine. Some animals were recorded acutely for confirmation of the status epilepticus (SE) and the presence of bilateral paroxysmal activity, as well as the appearance of interictal spikes and spontaneous seizures. Both drugs induced changes in the positioning and morphology of granular cells, regardless of whether they were generated before or after SE induction. However, only in the hippocampus ipsilateral to the KA injection, we observed granular layer dispersion and cell death in CA1 and CA3, although paroxysmal activity occurred in both hippocampi. Surprisingly, the injection of KA also led to an increase in the generation of astrocytes from DCX+ progenitors, which were generally considered as committed to a neuronal phenotype. In this model, we also observed cells with morphology and NSCs markers, suggesting that DCX+ progenitors could indeed revert to more primitive states in the cell lineage and generate astrocytes. In contrast, we observed an increase in neurogenesis in the opposite side to the injection of KA, as well as in both hippocampi of animals treated with pilocarpine. While the boost of gliogenesis in the ipsilateral side to KA injection was associated with a significant granular cell dispersion and the degeneration of GABAergic interneurons, none of these effects were observed in the contralateral epileptic hippocampi. Taken together, our results suggest that increased neuronal excitability induced by KA and pilocarpine have different effects on cell differentiation and phenotypic fate of pre-existing and newly generated neurons in the hippocampus. These observations indicate that different animal models of mTLE may be entirely distinct from the perspective of cellular transformations taking place in the hippocampus.

MEMBROS DA BANCA:
Interno - 1721223 - ADRIANO BRETANHA LOPES TORT
Interno - 1728817 - CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
Interno - 1243905 - DRAULIO BARROS DE ARAUJO
Presidente - 1674643 - MARCOS ROMUALDO COSTA