Dra. Luisa Rocha - Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats

31 de Mayo de 2023

Invitamos a leer el artículo: “Transcranial Focal Electric Stimulation Avoids P-GlycoproteinOver-Expression during Electrical Amygdala Kindling andDelays Epileptogenesis in Rats”, en la que colaboró la Doctora Luisa Rocha, Investigadora de Cinvestav Sede Sur

Autores: Daniel Fonseca Barriendos, José Luis Castañeda Cabral, Frida Martínez Cuevas, Walter Besio, Alejandro Valdés Cruz, y Luisa Rocha

Felicitamos al estudiantado y profesorado que contribuyeron en esta investigación por su arduo trabajo.

Abstract: Recent evidence suggests that P-glycoprotein (P-gp) overexpression mediates hyperex-citability and is associated with epileptogenesis. Transcranial focal electrical stimulation (TFS) delaysepileptogenesis and inhibits P-gp overexpression after a generalized seizure. Here, first we measuredP-gp expression during epileptogenesis and second, we assessed if TFS antiepileptogenic effect wasrelated with P-gp overexpression avoidance. Male Wistar rats were implanted in right basolateralamygdala and stimulated daily for electrical amygdala kindling (EAK), P-gp expression was as-sessed during epileptogenesis in relevant brain areas. Stage I group showed 85% increase in P-gpin ipsilateral hippocampus (p< 0.001). Stage III group presented 58% and 57% increase in P-gp inboth hippocampi (p< 0.05). Kindled group had 92% and 90% increase in P-gp in both hippocampi(p< 0.01), and 93% and 143% increase in both neocortices (p< 0.01). For the second experiment,TFS was administrated daily after each EAK stimulation for 20 days and P-gp concentration wasassessed. No changes were found in the TFS group (p> 0.05). Kindled group showed 132% and138% increase in P-gp in both hippocampi (p< 0.001) and 51% and 92% increase in both cortices(p< 0.001). Kindled + TFS group presented no changes (p> 0.05). Our experiments revealed thatprogression of EAK is associated with increased P-gp expression. These changes are structure-specificand dependent on seizure severity. EAK-induced P-gp overexpression would be associated withneuronal hyperexcitability and thus, epileptogenesis. P-gp could be a novel therapeutical target toavoid epileptogenesis. In accordance with this, TFS inhibited P-gp overexpression and interfered withEAK. An important limitation of the present study is that P-gp neuronal expression was not evaluatedunder the different experimental conditions. Future studies should be carried out to determineP-gp neuronal overexpression in hyperexcitable networks during epileptogenesis. The TFS-inducedlessening of P-gp overexpression could be a novel therapeutical strategy to avoid epileptogenesis inhigh-risk patients

Keywords: P-glycoprotein, epileptogenesis, neuromodulation, hippocampus, neocortex, kindling, TFS