Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats
Recent evidence suggests that P-glycoprotein (P-gp) overexpression mediates hyperexcitability and is associated with epileptogenesis. Transcranial focal electrical stimulation (TFS) delays epileptogenesis and inhibits P-gp overexpression after a generalized seizure. Here, first we measured P-gp expr...
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MDPI AG
2023-05-01
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| Online Access: | https://www.mdpi.com/2075-1729/13/6/1294 |
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| author | Daniel Fonseca-Barriendos José Luis Castañeda-Cabral Frida Martínez-Cuevas Walter Besio Alejandro Valdés-Cruz Luisa Rocha |
| author_facet | Daniel Fonseca-Barriendos José Luis Castañeda-Cabral Frida Martínez-Cuevas Walter Besio Alejandro Valdés-Cruz Luisa Rocha |
| author_sort | Daniel Fonseca-Barriendos |
| collection | DOAJ |
| description | Recent evidence suggests that P-glycoprotein (P-gp) overexpression mediates hyperexcitability and is associated with epileptogenesis. Transcranial focal electrical stimulation (TFS) delays epileptogenesis and inhibits P-gp overexpression after a generalized seizure. Here, first we measured P-gp expression during epileptogenesis and second, we assessed if TFS antiepileptogenic effect was related with P-gp overexpression avoidance. Male Wistar rats were implanted in right basolateral amygdala and stimulated daily for electrical amygdala kindling (EAK), P-gp expression was assessed during epileptogenesis in relevant brain areas. Stage I group showed 85% increase in P-gp in ipsilateral hippocampus (<i>p</i> < 0.001). Stage III group presented 58% and 57% increase in P-gp in both hippocampi (<i>p</i> < 0.05). Kindled group had 92% and 90% increase in P-gp in both hippocampi (<i>p</i> < 0.01), and 93% and 143% increase in both neocortices (<i>p</i> < 0.01). For the second experiment, TFS was administrated daily after each EAK stimulation for 20 days and P-gp concentration was assessed. No changes were found in the TFS group (<i>p</i> > 0.05). Kindled group showed 132% and 138% increase in P-gp in both hippocampi (<i>p</i> < 0.001) and 51% and 92% increase in both cortices (<i>p</i> < 0.001). Kindled + TFS group presented no changes (<i>p</i> > 0.05). Our experiments revealed that progression of EAK is associated with increased P-gp expression. These changes are structure-specific and dependent on seizure severity. EAK-induced P-gp overexpression would be associated with neuronal hyperexcitability and thus, epileptogenesis. P-gp could be a novel therapeutical target to avoid epileptogenesis. In accordance with this, TFS inhibited P-gp overexpression and interfered with EAK. An important limitation of the present study is that P-gp neuronal expression was not evaluated under the different experimental conditions. Future studies should be carried out to determine P-gp neuronal overexpression in hyperexcitable networks during epileptogenesis. The TFS-induced lessening of P-gp overexpression could be a novel therapeutical strategy to avoid epileptogenesis in high-risk patients. |
| first_indexed | 2024-03-11T02:14:52Z |
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| last_indexed | 2024-03-11T02:14:52Z |
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| spelling | doaj.art-d412a9eb96a749b98b995a07763a1d812023-11-18T11:17:19ZengMDPI AGLife2075-17292023-05-01136129410.3390/life13061294Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in RatsDaniel Fonseca-Barriendos0José Luis Castañeda-Cabral1Frida Martínez-Cuevas2Walter Besio3Alejandro Valdés-Cruz4Luisa Rocha5Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Ciudad de México C.P. 14330, MexicoDepartamento de Biología Celular y Molecular, Centro Universitrio de Ciencias Biológicas y Agropecuaias, Universidad de Guadalajara, Zapopan C.P. 44600, MexicoDepartamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Ciudad de México C.P. 14330, MexicoDepartment of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, RI 028881, USALaboratorio de Neurofisiología del Control y la Regulación, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Ciudad de México C.P. 14370, MexicoDepartamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Ciudad de México C.P. 14330, MexicoRecent evidence suggests that P-glycoprotein (P-gp) overexpression mediates hyperexcitability and is associated with epileptogenesis. Transcranial focal electrical stimulation (TFS) delays epileptogenesis and inhibits P-gp overexpression after a generalized seizure. Here, first we measured P-gp expression during epileptogenesis and second, we assessed if TFS antiepileptogenic effect was related with P-gp overexpression avoidance. Male Wistar rats were implanted in right basolateral amygdala and stimulated daily for electrical amygdala kindling (EAK), P-gp expression was assessed during epileptogenesis in relevant brain areas. Stage I group showed 85% increase in P-gp in ipsilateral hippocampus (<i>p</i> < 0.001). Stage III group presented 58% and 57% increase in P-gp in both hippocampi (<i>p</i> < 0.05). Kindled group had 92% and 90% increase in P-gp in both hippocampi (<i>p</i> < 0.01), and 93% and 143% increase in both neocortices (<i>p</i> < 0.01). For the second experiment, TFS was administrated daily after each EAK stimulation for 20 days and P-gp concentration was assessed. No changes were found in the TFS group (<i>p</i> > 0.05). Kindled group showed 132% and 138% increase in P-gp in both hippocampi (<i>p</i> < 0.001) and 51% and 92% increase in both cortices (<i>p</i> < 0.001). Kindled + TFS group presented no changes (<i>p</i> > 0.05). Our experiments revealed that progression of EAK is associated with increased P-gp expression. These changes are structure-specific and dependent on seizure severity. EAK-induced P-gp overexpression would be associated with neuronal hyperexcitability and thus, epileptogenesis. P-gp could be a novel therapeutical target to avoid epileptogenesis. In accordance with this, TFS inhibited P-gp overexpression and interfered with EAK. An important limitation of the present study is that P-gp neuronal expression was not evaluated under the different experimental conditions. Future studies should be carried out to determine P-gp neuronal overexpression in hyperexcitable networks during epileptogenesis. The TFS-induced lessening of P-gp overexpression could be a novel therapeutical strategy to avoid epileptogenesis in high-risk patients.https://www.mdpi.com/2075-1729/13/6/1294P-glycoproteinepileptogenesisneuromodulationhippocampusneocortexkindling |
| spellingShingle | Daniel Fonseca-Barriendos José Luis Castañeda-Cabral Frida Martínez-Cuevas Walter Besio Alejandro Valdés-Cruz Luisa Rocha Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats Life P-glycoprotein epileptogenesis neuromodulation hippocampus neocortex kindling |
| title | Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats |
| title_full | Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats |
| title_fullStr | Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats |
| title_full_unstemmed | Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats |
| title_short | Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats |
| title_sort | transcranial focal electric stimulation avoids p glycoprotein over expression during electrical amygdala kindling and delays epileptogenesis in rats |
| topic | P-glycoprotein epileptogenesis neuromodulation hippocampus neocortex kindling |
| url | https://www.mdpi.com/2075-1729/13/6/1294 |
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