Up-regulation of d-serine Might Induce GABAergic Neuronal Degeneration in the Cerebral Cortex and Hippocampus in the Mouse Pilocarpine Model of Epilepsy |
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Authors: | Yong-Hong Liu Lian Wang Li-Chun Wei Yuan-Gui Huang Liang-Wei Chen |
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Affiliation: | (1) Institute of Neurosciences, The Fourth Military Medical University, 710032 Xi’an, China;(2) Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China;(3) Department of Radiation Oncology Neurology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China |
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Abstract: | Epilepsy is a serious neurological disorder with neuronal loss and spontaneous recurrent seizures, but the neurochemical basis remains largely unclear. We hypothesize that d-serine, a newly identified endogenous co-agonist of N-methyl-d-aspartate (NMDA) receptor, may trigger excitotoxicity and neuronal damage in epileptogenesis. By using a mouse pilocarpine model, immunohistochemistry, Fluoro-Jade staining and double-labeling, the present study revealed up-regulation of d-serine expression in a proportion (41%) of neurons in the cerebral cortex and hippocampus. The d-serine-positive neurons occurred at 4 h, reached peak levels at 12–24 h, and gradually went down at 3–14 days. Moreover, most of d-serine-positive neurons were GABAergic (98%), underwent degenerating death (93%), and were accompanied enhancing phosphorylation of NMDA receptor subunit 1. This study has provided new evidence that up-regulation of d-serine production might induce GABAergic neuronal degeneration through excitotoxic mechanism in the pilocarpine model and may be involved in early pathogenesis and recurrent seizure of chronic epilepsy. Ms. L. Wang is on leave from Department of Neurology, Kunming General Hospital of Chengdu Military Region, China. |
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Keywords: | font-variant:small-caps" >d-serine Epilepsy GABAergic neurons Neurodegeneration Fluoro-Jade C staining |
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