Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy
José Luiz Liberato,
Lívea Dornela Godoy,
Alexandra Olimpio Siqueira Cunha,
Marcia Renata Mortari,
Rene de Oliveira Beleboni,
Andréia C. K. Fontana,
Norberto Peporine Lopes,
Wagner Ferreira dos Santos
Affiliations
José Luiz Liberato
Neurobiology and Venoms Laboratory (LNP), Department of Biology, College of Philosophy, Sciences and Literature of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14040-901 São Paulo, Brazil
Lívea Dornela Godoy
Neurobiology and Venoms Laboratory (LNP), Department of Biology, College of Philosophy, Sciences and Literature of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14040-901 São Paulo, Brazil
Alexandra Olimpio Siqueira Cunha
Neurobiology and Venoms Laboratory (LNP), Department of Biology, College of Philosophy, Sciences and Literature of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14040-901 São Paulo, Brazil
Marcia Renata Mortari
Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, DF 70910-900 Brasília, Brazil
Rene de Oliveira Beleboni
Department of Biotechnology/School of Medicine, University of Ribeirão Preto, Av. Costábile Romano, 2201, Ribeirão Preto, 14096-900 São Paulo, Brazil
Andréia C. K. Fontana
Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA 19102, USA
Norberto Peporine Lopes
NPPNS, Department of Physics and Chemistry, College of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil, Av. do Cafe s/n, Ribeirão Preto, 14040-903 São Paulo, Brazil
Wagner Ferreira dos Santos
Neurobiology and Venoms Laboratory (LNP), Department of Biology, College of Philosophy, Sciences and Literature of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14040-901 São Paulo, Brazil
Epilepsy is considered as one of the major disabling neuropathologies. Almost one third of adult patients with temporal lobe epilepsy (TLE) do not respond to current antiepileptic drugs (AEDs). Additionally, most AEDs do not have neuroprotective effects against the inherent neurodegenerative process underlying the hippocampal sclerosis on TLE. Dysfunctions in the GABAergic neurotransmission may contribute not only to the onset of epileptic activity but also constitute an important system for therapeutic approaches. Therefore, molecules that enhance GABA inhibitory effects could open novel avenues for the understanding of epileptic plasticity and for drug development. Parawixin2, a compound isolated from Parawixia bistriata spider venom, inhibits both GABA and glycine uptake and has an anticonvulsant effect against a wide range of chemoconvulsants. The neuroprotective potential of Parawixin2 was analyzed in a model of TLE induced by a long-lasting Status Epilepticus (SE), and its efficiency was compared to well-known neuroprotective drugs, such as riluzole and nipecotic acid. Neuroprotection was assessed through histological markers for cell density (Nissl), astrocytic reactivity (GFAP) and cell death labeling (TUNEL), which were performed 24 h and 72 h after SE. Parawixin2 treatment resulted in neuroprotective effects in a dose dependent manner at 24 h and 72 h after SE, as well as reduced reactive astrocytes and apoptotic cell death. Based on these findings, Parawixin2 has a great potential to be used as a tool for neuroscience research and as a probe to the development of novel GABAergic neuroprotective agents.
