2. Academic Validation
  3. CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy

CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy

  • Behav Brain Res. 2017 Mar 30;322(Pt A):83-91. doi: 10.1016/j.bbr.2017.01.014.
Zhike Zhou 1,  Tingting Liu 2,  Xiaoyu Sun 2,  Xiaopeng Mu 3,  Gang Zhu 4,  Ting Xiao 5,  Mei Zhao 6,  Chuansheng Zhao 7
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Neurology, People's Hospital of Liaoning Province, Shenyang, Liaoning, People's Republic of China.
  • 3 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.
  • 4 Department of Psychiatry, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, People's Republic of China.
  • 5 Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, Liaoning, People's Republic of China.
  • 6 Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang, Liaoning, People's Republic of China.
  • 7 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.
PMID: 28104461 DOI: 10.1016/j.bbr.2017.01.014
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.

Keywords

Enriched environment; Neurogenesis; Stromal cell-derived factor-1; Temporal lobe epilepsy.

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