Disease Modifying Effects of the Spider Toxin Parawixin2 in the Experimental Epilepsy Model

Author(s)

Godoy, Livea Dornela ^{[1, 2]} ; Liberato, Jose Luiz ^{[1, 2]} ; Batista Celani, Marcus Vinicius ^[1] ; Gobbo-Neto, Leonardo ^[3] ; Lopes, Norberto Peporine ^[3] ; dos Santos, Wagner Ferreira ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Lab Neurobiol & Peconhas LNP, Fac Filosofia Ciencias & Letras Ribeirao Preto, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Inst Neurociencias & Comportamento INEC, Av Cafe 2450, BR-14050220 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Nucleo Pesquisas Prod Nat & Sintet NPPNS, Fac Ciencias Farmaceut Ribeirao Preto, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: TOXINS; v. 9, n. 9 SEP 2017.
• Web of Science Citations: 3

Abstract

(1) Background: Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. It is also the one with the highest percentage of drug-resistance to the current available anti-epileptic drugs (AED). Additionaly, most antiepileptic drugs are only able to control seizures in epileptogenesis, but do not decrease the hippocampal neurodegenerative process. TLE patients have a reduced population of interneuronal cells, which express Parvalbumin (PV) proteins. This reduction is directly linked to seizure frequency and severity in the chronic period of epilepsy. There is therefore a need to seek new therapies with a disease-modifying profile, and with efficient antiepileptic and neuroprotective properties. Parawixin2, a compound isolated from the venom of the spider Parawixia bistriata, has been shown to inhibit GABA transporters (GAT) and to have acute anticonvulsant effects in rats. (2) Methods: In this work, we studied the effects of Parawixin2 and Tiagabine (an FDA- approved GAT inhibitor), and compared these effects in a TLE model. Rats were subjected to lithium-pilocarpine TLE model and the main features were evaluated over a chronic period including: (a) spontaneous recurrent seizures (SRS), (b) neuronal loss, and (c) PV cell density in different regions of the hippocampus (CA1, CA3, DG and Hilus). (3) Results: Parawixin2 treatment reduced SRS frequency whereas Tiagabine did not. We also found a significant reduction in neuronal loss in CA3 and in the hilus regions of the hippocampus, in animals treated with Parawixin2. Noteworthy, Parawixin2 significantly reversed PV cell loss observed particularly in DG layers. (4) Conclusions: Parawixin2 exerts a promising neuroprotective and anti-epileptic effect and has potential as a novel agent in drug design. (AU)