Purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsy
Epilepsy is one of the most prevalent neurological disorders globally. Current treatments mainly target neuronal activity, often overlooking the involvement of astrocytes and microglia in epilepsy’s pathophysiology. Here, we explored the impact of purinergic receptors, predominantly found in glial t...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1513135/full |
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| author | Nelson Espinosa Soraya Martín-Suárez Ariel Lara-Vasquez Trinidad Montero Teresa Muro-García German Fernandez Juan Manuel Encinas-Pérez Juan Manuel Encinas-Pérez Juan Manuel Encinas-Pérez Pablo Fuentealba |
| author_facet | Nelson Espinosa Soraya Martín-Suárez Ariel Lara-Vasquez Trinidad Montero Teresa Muro-García German Fernandez Juan Manuel Encinas-Pérez Juan Manuel Encinas-Pérez Juan Manuel Encinas-Pérez Pablo Fuentealba |
| author_sort | Nelson Espinosa |
| collection | DOAJ |
| description | Epilepsy is one of the most prevalent neurological disorders globally. Current treatments mainly target neuronal activity, often overlooking the involvement of astrocytes and microglia in epilepsy’s pathophysiology. Here, we explored the impact of purinergic receptors, predominantly found in glial tissue, on epileptiform activity. We used TNP-ATP, a potent purinergic receptor antagonist, and conducted experiments using a mouse model of mesial temporal lobe epilepsy to examine behavioral performance and neural activity patterns. Our findings reveal that although TNP-ATP treatment did not significantly impact motor function or anxiety levels, it reduced both the amplitude and rate of hippocampal interictal discharges. Such reduction also affected the synchrony of associated neuronal spiking. Additionally, cognitive function, particularly hippocampus-dependent spatial memory and prefrontal cortex-dependent executive control, were partially restored. Moreover, neuronal recordings showed increased phase coherence between the hippocampus and prefrontal cortex for both slow (theta) and fast (gamma) oscillations in treated animals, indicating strengthened neural coordination between cortical regions upon purinergic receptor antagonism. These results underscore the potential role of purinergic receptor antagonists in improving behavioral and cognitive performance in epilepsy, providing novel insight into the use of these pharmacological agents as a therapeutic approach. |
| format | Article |
| id | doaj-art-250f10ac6d9e402dbe3f58e62db27bba |
| institution | OA Journals |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-250f10ac6d9e402dbe3f58e62db27bba2025-08-20T02:25:12ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-04-011910.3389/fnins.2025.15131351513135Purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsyNelson Espinosa0Soraya Martín-Suárez1Ariel Lara-Vasquez2Trinidad Montero3Teresa Muro-García4German Fernandez5Juan Manuel Encinas-Pérez6Juan Manuel Encinas-Pérez7Juan Manuel Encinas-Pérez8Pablo Fuentealba9Departamento de Psiquiatria, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileAchucarro Basque Center for Neuroscience, Leioa, Bizkaia, SpainDepartamento de Psiquiatria, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Psiquiatria, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileAchucarro Basque Center for Neuroscience, Leioa, Bizkaia, SpainDepartamento de Psiquiatria, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileAchucarro Basque Center for Neuroscience, Leioa, Bizkaia, SpainIKERBASQUE, Basque Foundation for Science, Bilbao, Bizkaia, SpainDepartment of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country, Leioa, Bizkaia, SpainDepartamento de Psiquiatria, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileEpilepsy is one of the most prevalent neurological disorders globally. Current treatments mainly target neuronal activity, often overlooking the involvement of astrocytes and microglia in epilepsy’s pathophysiology. Here, we explored the impact of purinergic receptors, predominantly found in glial tissue, on epileptiform activity. We used TNP-ATP, a potent purinergic receptor antagonist, and conducted experiments using a mouse model of mesial temporal lobe epilepsy to examine behavioral performance and neural activity patterns. Our findings reveal that although TNP-ATP treatment did not significantly impact motor function or anxiety levels, it reduced both the amplitude and rate of hippocampal interictal discharges. Such reduction also affected the synchrony of associated neuronal spiking. Additionally, cognitive function, particularly hippocampus-dependent spatial memory and prefrontal cortex-dependent executive control, were partially restored. Moreover, neuronal recordings showed increased phase coherence between the hippocampus and prefrontal cortex for both slow (theta) and fast (gamma) oscillations in treated animals, indicating strengthened neural coordination between cortical regions upon purinergic receptor antagonism. These results underscore the potential role of purinergic receptor antagonists in improving behavioral and cognitive performance in epilepsy, providing novel insight into the use of these pharmacological agents as a therapeutic approach.https://www.frontiersin.org/articles/10.3389/fnins.2025.1513135/fullpurinergic receptortemporal lobe epilepsyinterictal dischargescognitive dysfunctioncortical oscillation |
| spellingShingle | Nelson Espinosa Soraya Martín-Suárez Ariel Lara-Vasquez Trinidad Montero Teresa Muro-García German Fernandez Juan Manuel Encinas-Pérez Juan Manuel Encinas-Pérez Juan Manuel Encinas-Pérez Pablo Fuentealba Purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsy Frontiers in Neuroscience purinergic receptor temporal lobe epilepsy interictal discharges cognitive dysfunction cortical oscillation |
| title | Purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsy |
| title_full | Purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsy |
| title_fullStr | Purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsy |
| title_full_unstemmed | Purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsy |
| title_short | Purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsy |
| title_sort | purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsy |
| topic | purinergic receptor temporal lobe epilepsy interictal discharges cognitive dysfunction cortical oscillation |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1513135/full |
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