Calpain protease mediates axonal degeneration induced in a model of Status epilepticus.

UNSAIN, NICOLÁS; BARKER, PHILIP; DANELON, VÍCTOR

Rio de Janeiro

Congreso; IBRO Congress 2015; 2015

Recent findings indicate that the mechanisms which drive reshaping of the nervous system are aberrantly activated in neurodegenerative diseases. Epilepsy is a neurodegenerative disease that affects between 1 and 2% of the world population, characterized by recurrent seizures. This causes permanent neurological damage, resulting in cognitive dysfunction and other serious neurological conditions. There are several Status Epilepticus models (SE), ranging from in vivo to in vitro models. In this study, we used an in vitro model of SE in which hippocampal bulk cultures and pure samples of axons undergoing degeneration, were analyzed to reveal if calpains activation induced biochemical and morphological changes in axons after excitotoxicity. We observed that several calpains subtracts, such as α-spectrin, neurofilament M, begin to be processed during the excitotoxic insult, and the neurotrophin receptor, TrkB and pro-Caspase 3 begin to be processed 3 hours after the insult was finished. The degradation rate of this protein (except for proCaspase 3) is faster in the axonal compartment than the soma. When α-spectrin, neurofilament M were completely processed in the axonal fraction, on contrast, theTrkB-tr isoform was significantly increased. We further show that the treatment with ALLN, a specific Calpain activity blocker, completely protects the neuronal processes from degeneration and induce neuroprotection. These results indicate that the protease calpain is a key element in neuronal degeneration induces by seizures.