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

• Published in: Toxins Vol. 9; no. 9; p. 262
• Main Authors: Godoy, Lívea Dornela, Liberato, José Luiz, Celani, Marcus Vinícius Batista, Gobbo-Neto, Leonardo, Lopes, Norberto Peporine, Dos Santos, Wagner Ferreira
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-08-2017; MDPI
• Subjects: Adults; Animals; Anticonvulsants; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Antiepileptic agents; Cell density; Convulsions & seizures; Disease Models, Animal; Drug development; Drug resistance; Epilepsy; Epilepsy, Temporal Lobe - chemically induced; Epilepsy, Temporal Lobe - drug therapy; GABA transporter inhibitor; Hippocampus; Hippocampus - drug effects; Lithium; lithium-pilocarpine model; Male; Neurons - drug effects; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurotransmitter Uptake Inhibitors - pharmacology; Neurotransmitter Uptake Inhibitors - therapeutic use; Nipecotic Acids - pharmacology; Nipecotic Acids - therapeutic use; Parawixia bistriata; Parvalbumin; Photovoltaic cells; Pilocarpine; Proteins; Rats; Rats, Wistar; Reduction; Seizing; Seizures; Solar cells; Spider toxin; Spider Venoms - pharmacology; Spider Venoms - therapeutic use; Stability; Temporal lobe; temporal lobe epilepsy; Tiagabine; Toxins; Urea - analogs & derivatives; Urea - pharmacology; Urea - therapeutic use; Venom; Tiagabine; temporal lobe epilepsy; hippocampus; lithium-pilocarpine model; neuroprotection; GABA transporter inhibitor; Spider toxin; Parawixia bistriata; Parvalbumin
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins9090262

(1)
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
, has been shown to inhibit GABA transporters (GAT) and to have acute anticonvulsant effects in rats. (2)
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)
Parawixin2 treatment reduced SRS frequency whereas Tiagabine did not. We also found a significant reduction in neuronal loss in CA3 and in the
of the hippocampus, in animals treated with Parawixin2. Noteworthy, Parawixin2 significantly reversed PV cell loss observed particularly in DG layers. (4)
Parawixin2 exerts a promising neuroprotective and anti-epileptic effect and has potential as a novel agent in drug design.