Up-regulation of D-serine might induce GABAergic neuronal degeneration in the cerebral cortex and hippocampus in the mouse pilocarpine model of epilepsy.
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.
Liu
Yong-Hong
YH
Institute of Neurosciences, The Fourth Military Medical University, 710032, Xi'an, China.
Wang
Lian
L
Wei
Li-Chun
LC
Huang
Yuan-Gui
YG
Chen
Liang-Wei
LW
D000818:Animals; D016923:Cell Death; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced*; D010862:Pilocarpine; D018079:Receptors, GABA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013237:Stereoisomerism; D015854:Up-Regulation
D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine; D012694:Serine