Locally Reducing KCC2 Activity in the Hippocampus is Sufficient to Induce Temporal Lobe Epilepsy
| Autor: | Joshua L. Smalley, Peter M. Andrew, Stephen J. Moss, Matt R. Kelley, Tarek Z. Deeb, Thomas A. Ollerhead, Ross A. Cardarelli, Nicholas J. Brandon |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Genotype KCC2 Genetic Vectors Local ablation lcsh:Medicine Hippocampus General Biochemistry Genetics and Molecular Biology Temporal lobe GABA 03 medical and health sciences Epilepsy 0302 clinical medicine Animals Humans Medicine Pathological gamma-Aminobutyric Acid Neurons lcsh:R5-920 Hippocampal sclerosis Symporters business.industry lcsh:R General Medicine medicine.disease Pathophysiology nervous system diseases Disease Models Animal 030104 developmental biology Epilepsy Temporal Lobe Female Gabaergic inhibition lcsh:Medicine (General) business Neuroscience 030217 neurology & neurosurgery Research Paper |
| Zdroj: | EBioMedicine, Vol 32, Iss, Pp 62-71 (2018) EBioMedicine |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2018.05.029 |
| Popis: | Mesial temporal lobe epilepsy (mTLE) is the most common form of epilepsy, believed to arise in part from compromised GABAergic inhibition. The neuronal specific K+/Cl− co-transporter 2 (KCC2) is a critical determinant of the efficacy of GABAergic inhibition and deficits in its activity are observed in mTLE patients and animal models of epilepsy. To test if reductions of KCC2 activity directly contribute to the pathophysiology of mTLE, we locally ablated KCC2 expression in a subset of principal neurons within the adult hippocampus. Deletion of KCC2 resulted in compromised GABAergic inhibition and the development of spontaneous, recurrent generalized seizures. Moreover, local ablation of KCC2 activity resulted in hippocampal sclerosis, a key pathological change seen in mTLE. Collectively, our results demonstrate that local deficits in KCC2 activity within the hippocampus are sufficient to precipitate mTLE. Keywords: KCC2, GABA, Epilepsy, Hippocampal sclerosis |
| Databáze: | OpenAIRE |
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