GABAA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy Onset
Enhanced spontaneous GABAA receptor activity is associated with focal cortical dysplasia (FCD), a developmental malformation of the cerebral cortex. Clinical manifestations in FCD vary with age at epilepsy onset with a more favorable prognosis in patients with late-onset (LO) compared to that in cas...
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.562811/full |
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| author | Jyotirmoy Banerjee Soumil Dey Aparna Banerjee Dixit Ramesh Doddamani Meher Chand Sharma Ajay Garg P. Sarat Chandra Manjari Tripathi |
| author_facet | Jyotirmoy Banerjee Soumil Dey Aparna Banerjee Dixit Ramesh Doddamani Meher Chand Sharma Ajay Garg P. Sarat Chandra Manjari Tripathi |
| author_sort | Jyotirmoy Banerjee |
| collection | DOAJ |
| description | Enhanced spontaneous GABAA receptor activity is associated with focal cortical dysplasia (FCD), a developmental malformation of the cerebral cortex. Clinical manifestations in FCD vary with age at epilepsy onset with a more favorable prognosis in patients with late-onset (LO) compared to that in cases with early-onset (EO). This study was designed to test the hypothesis in FCD that spontaneous GABAA receptor-mediated epileptogenicity depends on the age at epilepsy onset and varies between patients with early and late-onset age in FCD. To this end, brain specimens were obtained from the maximal spiking region (MAX) and minimal spiking region (MIN) of the epileptic foci of EO (n = 14, mean age = 10.6 ± 2.9 years) and LO (n = 10, mean age = 27 ± 5.6 years) patients undergoing electrocorticography (ECoG) guided surgery. The whole-cell patch-clamp technique was used to record spontaneous GABAergic currents from normal-looking pyramidal neurons in slice preparations of resected brain samples. We detected higher frequency and amplitude of GABAergic events in MAX samples compared to MIN samples of LO patients, while they were comparable in MIN and MAX samples of EO patients. Further GABAergic activity in the MIN and MAX samples of EO patients was higher than the MIN samples of LO patients. This suggests that in LO patients, GABAA receptor-mediated epileptogenicity is confined only to the high spiking areas, but in EO patients, it affects low spiking regions as well. |
| first_indexed | 2024-12-14T21:44:12Z |
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| id | doaj.art-2f2676dabcf249f39aba0934ac35eb63 |
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| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-14T21:44:12Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-2f2676dabcf249f39aba0934ac35eb632022-12-21T22:46:23ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-09-011410.3389/fncel.2020.562811562811GABAA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy OnsetJyotirmoy Banerjee0Soumil Dey1Aparna Banerjee Dixit2Ramesh Doddamani3Meher Chand Sharma4Ajay Garg5P. Sarat Chandra6Manjari Tripathi7Department of Biophysics, All India Institute of Medical Sciences, New Delhi, IndiaDepartment of Neurosurgery, All India Institute of Medical Sciences, New Delhi, IndiaDr. B R Ambedkar Centre for Biomedical Research, University of Delhi, New Delhi, IndiaDepartment of Neurosurgery, All India Institute of Medical Sciences, New Delhi, IndiaDepartment of Neuropathology, All India Institute of Medical Sciences, New Delhi, IndiaDepartment of Neuroimaging and Interventional Neuroradiology, All India Institute of Medical Sciences, New Delhi, IndiaDepartment of Neurosurgery, All India Institute of Medical Sciences, New Delhi, IndiaDepartment of Neurology, All India Institute of Medical Sciences, New Delhi, IndiaEnhanced spontaneous GABAA receptor activity is associated with focal cortical dysplasia (FCD), a developmental malformation of the cerebral cortex. Clinical manifestations in FCD vary with age at epilepsy onset with a more favorable prognosis in patients with late-onset (LO) compared to that in cases with early-onset (EO). This study was designed to test the hypothesis in FCD that spontaneous GABAA receptor-mediated epileptogenicity depends on the age at epilepsy onset and varies between patients with early and late-onset age in FCD. To this end, brain specimens were obtained from the maximal spiking region (MAX) and minimal spiking region (MIN) of the epileptic foci of EO (n = 14, mean age = 10.6 ± 2.9 years) and LO (n = 10, mean age = 27 ± 5.6 years) patients undergoing electrocorticography (ECoG) guided surgery. The whole-cell patch-clamp technique was used to record spontaneous GABAergic currents from normal-looking pyramidal neurons in slice preparations of resected brain samples. We detected higher frequency and amplitude of GABAergic events in MAX samples compared to MIN samples of LO patients, while they were comparable in MIN and MAX samples of EO patients. Further GABAergic activity in the MIN and MAX samples of EO patients was higher than the MIN samples of LO patients. This suggests that in LO patients, GABAA receptor-mediated epileptogenicity is confined only to the high spiking areas, but in EO patients, it affects low spiking regions as well.https://www.frontiersin.org/article/10.3389/fncel.2020.562811/fulldrug-resistant epilepsyGABAergic activityelectrocorticography (ECoG)resected brain samplepatch-clamp technique |
| spellingShingle | Jyotirmoy Banerjee Soumil Dey Aparna Banerjee Dixit Ramesh Doddamani Meher Chand Sharma Ajay Garg P. Sarat Chandra Manjari Tripathi GABAA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy Onset Frontiers in Cellular Neuroscience drug-resistant epilepsy GABAergic activity electrocorticography (ECoG) resected brain sample patch-clamp technique |
| title | GABAA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy Onset |
| title_full | GABAA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy Onset |
| title_fullStr | GABAA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy Onset |
| title_full_unstemmed | GABAA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy Onset |
| title_short | GABAA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy Onset |
| title_sort | gabaa receptor mediated epileptogenicity in focal cortical dysplasia fcd depends on age at epilepsy onset |
| topic | drug-resistant epilepsy GABAergic activity electrocorticography (ECoG) resected brain sample patch-clamp technique |
| url | https://www.frontiersin.org/article/10.3389/fncel.2020.562811/full |
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