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Toxins 2017, 9(9), 262; https://doi.org/10.3390/toxins9090262

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

1
Laboratório de Neurobiologia e Peçonhas (LNP), Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, CEP 14040-901 Ribeirão Preto, São Paulo, Brazil
2
Instituto de Neurociências e Comportamento (INEC), Av. do Café, 2450, CEP 14050-220 Ribeirão Preto, São Paulo, Brazil
3
Núcleo de Pesquisas em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Cafe s/n, CEP 14040-903 Ribeirão Preto, São Paulo, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Eivind Undheim
Received: 12 January 2017 / Revised: 27 April 2017 / Accepted: 18 August 2017 / Published: 25 August 2017
(This article belongs to the Section Animal Venoms)
Full-Text   |   PDF [6776 KB, uploaded 25 August 2017]   |  

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. View Full-Text
Keywords: lithium-pilocarpine model; temporal lobe epilepsy; Parvalbumin; GABA transporter inhibitor; neuroprotection; hippocampus; Spider toxin; Parawixia bistriata; Tiagabine lithium-pilocarpine model; temporal lobe epilepsy; Parvalbumin; GABA transporter inhibitor; neuroprotection; hippocampus; Spider toxin; Parawixia bistriata; Tiagabine
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Godoy, L.D.; Liberato, J.L.; Celani, M.V.B.; Gobbo-Neto, L.; Lopes, N.P.; dos Santos, W.F. Disease Modifying Effects of the Spider Toxin Parawixin2 in the Experimental Epilepsy Model. Toxins 2017, 9, 262.

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