Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy
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...
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MDPI AG
2018-11-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/10/12/486 |
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| author | 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 |
| author_facet | 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 |
| author_sort | José Luiz Liberato |
| collection | DOAJ |
| description | 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 <i>Parawixia bistriata</i> 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. |
| first_indexed | 2024-04-11T22:15:04Z |
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| language | English |
| last_indexed | 2024-04-11T22:15:04Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-fdd5ed9d2e434e1ca3bc74f07c98105a2022-12-22T04:00:27ZengMDPI AGToxins2072-66512018-11-01101248610.3390/toxins10120486toxins10120486Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe EpilepsyJosé Luiz Liberato0Lívea Dornela Godoy1Alexandra Olimpio Siqueira Cunha2Marcia Renata Mortari3Rene de Oliveira Beleboni4Andréia C. K. Fontana5Norberto Peporine Lopes6Wagner Ferreira dos Santos7Neurobiology 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, BrazilNeurobiology 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, BrazilNeurobiology 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, BrazilLaboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, DF 70910-900 Brasília, BrazilDepartment of Biotechnology/School of Medicine, University of Ribeirão Preto, Av. Costábile Romano, 2201, Ribeirão Preto, 14096-900 São Paulo, BrazilDepartment of Pharmacology and Physiology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA 19102, USANPPNS, 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, BrazilNeurobiology 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, BrazilEpilepsy 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 <i>Parawixia bistriata</i> 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.https://www.mdpi.com/2072-6651/10/12/486spider toxin<i>Parawixia bistriata</i>Parawixin2GABA uptake inhibitortemporal lobe epilepsypilocarpine modelhippocampal lost cellsneuroprotection |
| spellingShingle | 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 Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy Toxins spider toxin <i>Parawixia bistriata</i> Parawixin2 GABA uptake inhibitor temporal lobe epilepsy pilocarpine model hippocampal lost cells neuroprotection |
| title | Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy |
| title_full | Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy |
| title_fullStr | Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy |
| title_full_unstemmed | Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy |
| title_short | Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy |
| title_sort | parawixin2 protects hippocampal cells in experimental temporal lobe epilepsy |
| topic | spider toxin <i>Parawixia bistriata</i> Parawixin2 GABA uptake inhibitor temporal lobe epilepsy pilocarpine model hippocampal lost cells neuroprotection |
| url | https://www.mdpi.com/2072-6651/10/12/486 |
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