title: CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy.
abstract: It has been showed that enriched environment (EE) enhances the hippocampal neurogenesis and improves the cognitive impairments, accompanied by the increased expressions of stromal cell-derived factor-1 (SDF-1) in adult rats of temporal lobe epilepsy (TLE). We examined whether the enhanced neurogenesis and improved cognitive functions induced by EE following seizures were mediated by SDF-1/CXCR4 pathway. Therefore, we investigated the effects of the EE combined with CXCR4 antagonist AMD3100 on neurogenesis, cognitive functions and the long-term seizure activity in the TLE model. Adult rats were randomly assigned as control rats, rats treated with EE, rats subjected to status epilepticus (SE), post-SE rats treated with EE, AMD3100 or EE combined with AMD3100 respectively. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the frequency and mean duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze test. EE treatment significantly, as well as improved cognitive impairments and decreased long-term seizure activity, and that these effects might be mediated through SDF-1/CXCR4 pathway during the chronic stage of TLE. Although AMD3100 reversed the effect of EE on neurogenesis, it did not abolish the cognitive improvement induced by EE following seizures. More importantly, EE combined with AMD3100 treatment significantly suppressed long-term seizure activity, which provided promising evidences to treat TLE.
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, People's Republic of China.
authors.forename: Zhike
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Neurology, People's Hospital of Liaoning Province, Shenyang, Liaoning, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Neurology, People's Hospital of Liaoning Province, Shenyang, Liaoning, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, People's Republic of China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Mu
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, Liaoning, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, People's Republic of China. Electronic address: cszhao@mail.cmu.edu.cn.
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001596:Benzylamines; D054377:Chemokine CXCL12 / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D000080027:Cyclams; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006799:Housing, Animal; D007608:Kainic Acid; D008297:Male; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011897:Random Allocation; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology
chemical_list: D000927:Anticonvulsants; D001596:Benzylamines; C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor; D007608:Kainic Acid
keywords: Enriched environment; Neurogenesis; Stromal cell-derived factor-1; Temporal lobe epilepsy