title: Co-activation of synaptic and extrasynaptic NMDA receptors by neuronal insults determines cell death in acute brain slice.
abstract: Overactivation of NMDA receptors is linked to cell death during neuronal insults. However the precise role of synaptic and extrasynaptic NMDA receptors remains to be further determined. In this study, we used the acute brain slice to examine the contributions of synaptic and extrasynaptic NMDA receptors to neuronal death. By activation of synaptic NMDA receptors with bath application of 100 μM bicuculline in acute brain slices, we observed a significant up-regulation in activation of neuronal survival-related signaling (p-CREB, p-ERK1/2 and p-AKT), without an obvious increase of LDH release and neuronal death. Interestingly, activation of extrasynaptic NMDA receptors alone by high dose of glutamate (200 μM) following blockade of synaptic NMDA receptors with co-application of 20 μM MK801 and 100 μM bicuculline, we failed to observe inhibition of neuronal survival signaling and neuronal damage. In contrast, co-activation of synaptic and extrasynaptic NMDA receptors by applying 200 μM glutamate or oxygen-glucose deprivation (OGD) to acute brain slices for 30 min, we observed a significant inhibition of CREB, ERK1/2 and AKT activation, an increase of LDH release and neuronal condensation. Together, co-activation of synaptic and extrasynaptic NMDA receptors by neuronal insults contributes to cell death in acute brain slice.
authors.affiliation: Department of Neurology, Laboratory of Neurological Diseases, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, Jiangsu 213003, China.
authors.forename: Zhuoyou
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, Foshan First People's Hospital, The Affiliated Foshan Hospital of Zhongshan University, 81 North Lingnan Avenue, Chancheng District, Foshan, Guangdong 52800, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Laboratory of Neurological Diseases, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, Jiangsu 213003, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Neuroscience Program, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, Laboratory of Neurological Diseases, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, Jiangsu 213003, China. Electronic address: xjyww@sina.com.
authors.forename: Weiwen
authors.initials: W
authors.lastname: Yun
authors.affiliation: Department of Neurology, Laboratory of Neurological Diseases, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, Jiangsu 213003, China. Electronic address: hippocampus2007@gmail.com.
authors.forename: Xianju
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D001640:Bicuculline
keywords: Brain slice; Excitotoxicity; Extrasynaptic NMDA receptors; Glutamate; Synaptic NMDA receptors