title: N-methyl-D-aspartate receptor NR2B subunit involved in depression-like behaviours in lithium chloride-pilocarpine chronic rat epilepsy model.
abstract: Depression is a common comorbidity in patients with epilepsy with unclear mechanisms. This study is to explore the role of glutamate N-methyl-D-aspartate (NMDA) receptor NR1, NR2A and NR2B subunits in epilepsy-associated depression. Lithium chloride (Licl)-pilocarpine chronic rat epilepsy model was established and rats were divided into epilepsy with depression (EWD) and epilepsy without depression (EWND) subgroups based on forced swim test. Expression of NMDA receptor NR1, NR2A and NR2B subunits was measured by western blot and immunofluorescence methods. The immobility time (IMT) was significantly greater in Licl-pilocarpine model group than in Control group, which was also greater in EWD group than in EWND group. No differences of spontaneous recurrent seizure (SRS) counts over two weeks and latency were found between EWD and EWND groups. The number of NeuN positive cells was significantly less in Licl-pilocarpine model group than in Control group, but had no difference between EWD and EWND groups. The ratios of phosphorylated NR1 (p-NR1)/NR1 and p-NR2B/NR2B were significantly greater in the hippocampus in EWD group than in EWND group. Moreover, the expression of p-NR1 and p-NR2B in the CA1 subfield of hippocampus were both greater in Licl-pilocarpine model group than Control group. Selective blockage of NR2B subunit with ifenprodil could alleviate depression-like behaviours of Licl-pilocarpine rat epilepsy model. In conclusion, glutamate NMDA receptor NR2B subunit was involved in promoting depression-like behaviours in the Licl-pilocarpine chronic rat epilepsy model and might be a target for treating epilepsy-associated depression.
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: peng.weifeng@zs-hospital.sh.cn.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Peng
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: ding.jing@zs-hospital.sh.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: li.xin2@zs-hospital.sh.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Emergency, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: fan.fan@zs-hospital.sh.cn.
authors.forename: Fan
authors.initials: F
authors.lastname: Fan
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: zhang.qianqian@zs-hospital.sh.cn.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China; The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China. Electronic address: wang.xin@zs-hospital.sh.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002908:Chronic Disease; D003866:Depressive Disorder / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D018021:Lithium Chloride; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010766:Phosphorylation; D010862:Pilocarpine; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012640:Seizures / Q000503:physiopathology / Q000523:psychology
chemical_list: D034961:Antigens, Nuclear; D018021:Lithium Chloride; D009419:Nerve Tissue Proteins; D010862:Pilocarpine; D016194:Receptors, N-Methyl-D-Aspartate; C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; C546339:Rbfox3 protein, rat
keywords: Depression; Epilepsy; Glutamate; N-methyl-d-aspartate receptor; NR2B subunit