Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy

Autor(es)

Liberato, Jose Luiz ^{[1, 2]} ; Godoy, Livea Dornela ^{[1, 2]} ; Siqueira Cunha, Alexandra Olimpio ^[1] ; Mortari, Marcia Renata ^[3] ; Beleboni, Rene de Oliveira ^[4] ; Fontana, Andreia C. K. ^[5] ; Lopes, Norberto Peporine ^[6] ; dos Santos, Wagner Ferreira ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Neurobiol & Venoms Lab LNP, Dept Biol, Coll Philosophy Sci & Literature Ribeirao Preto, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Neurosci Behav Inst INEC, Av Cafe 2450, BR-14050220 Ribeirao Preto, SP - Brazil

^[3] Univ Brasilia, Lab Neuropharmacol, Dept Physiol Sci, Inst Biol Sci, DF-70910900 Brasilia, DF - Brazil

^[4] Univ Ribeirao Preto, Sch Med, Dept Biotechnol, Av Costabile Romano 2201, BR-14096900 Ribeirao Preto, SP - Brazil

^[5] Drexel Univ, Coll Med, Dept Pharmacol & Physiol, 245 N 15th St, Philadelphia, PA 19102 - USA

^[6] Univ Sao Paulo, Coll Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, NPPNS, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 10, n. 12 DEC 2018.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 05/60254-0 - Avaliação da atividade neuroprotetora e anticonvulsivante do composto poliamínico FrPbA2 isolado da peçonha da aranha P. bistriata, em ratos Wistar submetidos ao Status Epilepticus induzido por pilocarpina intra-hipocampal
• Beneficiário: Wagner Ferreira dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular