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Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice.
Behav Brain Res 2015; 288:1-10BB

Abstract

Chronic restraint stress (CRS) causes hippocampal neurodegeneration and hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective effects and we have previously shown that flupirtine can protect against memory impairment induced by acute stress. The present study aimed to investigate whether flupirtine could alleviate spatial learning and memory impairment and hippocampal apoptosis induced by CRS. CRS mice were restrained in well-ventilated Plexiglass tubes for 6h daily beginning from 10:00 to 16:00 for 21 consecutive days. Mice were injected with flupirtine (10mg/kg and 25mg/kg) or vehicle (10% DMSO) 30min before restraint stress for 21 days. After stressor cessation, the spatial learning and memory, dendritic spine density, injured neurons and the levels of Bcl-2, Bax, p-Akt, p-GSK-3β, p-Erk1/2 and synaptophysin of hippocampal tissues were examined. Our results showed that flupirtine significantly prevented spatial learning and memory impairment induced by CRS in the Morris water maze. In addition, flupirtine (10mg/kg and 25mg/kg) treatment alleviated neuronal apoptosis and the reduction of dendritic spine density and synaptophysin expression in the hippocampal CA1 region of CRS mice. Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3β, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice. These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3β and Erk1/2 signaling pathways.

Authors+Show Affiliations

Department of Pharmacology, School of Basic Medicine, Tongji medical college, Huazhong University of Science and Technology, Wuhan 430030, China.Department of Pharmacology, School of Basic Medicine, Tongji medical college, Huazhong University of Science and Technology, Wuhan 430030, China.Department of Pharmacology, School of Basic Medicine, Tongji medical college, Huazhong University of Science and Technology, Wuhan 430030, China.Department of Pharmacology, School of Basic Medicine, Tongji medical college, Huazhong University of Science and Technology, Wuhan 430030, China.Department of Pharmacology, School of Basic Medicine, Tongji medical college, Huazhong University of Science and Technology, Wuhan 430030, China.Department of Pharmacology, School of Basic Medicine, Tongji medical college, Huazhong University of Science and Technology, Wuhan 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Pharmacology, School of Basic Medicine, Tongji medical college, Huazhong University of Science and Technology, Wuhan 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Pharmacology, School of Basic Medicine, Tongji medical college, Huazhong University of Science and Technology, Wuhan 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: xulinxu@hust.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25869780

Citation

Huang, Pengcheng, et al. "Flupirtine Attenuates Chronic Restraint Stress-induced Cognitive Deficits and Hippocampal Apoptosis in Male Mice." Behavioural Brain Research, vol. 288, 2015, pp. 1-10.
Huang P, Li C, Fu T, et al. Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice. Behav Brain Res. 2015;288:1-10.
Huang, P., Li, C., Fu, T., Zhao, D., Yi, Z., Lu, Q., ... Xu, X. (2015). Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice. Behavioural Brain Research, 288, pp. 1-10. doi:10.1016/j.bbr.2015.04.004.
Huang P, et al. Flupirtine Attenuates Chronic Restraint Stress-induced Cognitive Deficits and Hippocampal Apoptosis in Male Mice. Behav Brain Res. 2015 Jul 15;288:1-10. PubMed PMID: 25869780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice. AU - Huang,Pengcheng, AU - Li,Cai, AU - Fu,Tianli, AU - Zhao,Dan, AU - Yi,Zhen, AU - Lu,Qing, AU - Guo,Lianjun, AU - Xu,Xulin, Y1 - 2015/04/11/ PY - 2014/11/25/received PY - 2015/04/01/revised PY - 2015/04/04/accepted PY - 2015/4/15/entrez PY - 2015/4/15/pubmed PY - 2016/1/28/medline KW - Akt (protein kinase B) KW - Chronic restraint stress KW - Cognitive impairment KW - Flupirtine KW - Glycogen synthase kinase 3 beta SP - 1 EP - 10 JF - Behavioural brain research JO - Behav. Brain Res. VL - 288 N2 - Chronic restraint stress (CRS) causes hippocampal neurodegeneration and hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective effects and we have previously shown that flupirtine can protect against memory impairment induced by acute stress. The present study aimed to investigate whether flupirtine could alleviate spatial learning and memory impairment and hippocampal apoptosis induced by CRS. CRS mice were restrained in well-ventilated Plexiglass tubes for 6h daily beginning from 10:00 to 16:00 for 21 consecutive days. Mice were injected with flupirtine (10mg/kg and 25mg/kg) or vehicle (10% DMSO) 30min before restraint stress for 21 days. After stressor cessation, the spatial learning and memory, dendritic spine density, injured neurons and the levels of Bcl-2, Bax, p-Akt, p-GSK-3β, p-Erk1/2 and synaptophysin of hippocampal tissues were examined. Our results showed that flupirtine significantly prevented spatial learning and memory impairment induced by CRS in the Morris water maze. In addition, flupirtine (10mg/kg and 25mg/kg) treatment alleviated neuronal apoptosis and the reduction of dendritic spine density and synaptophysin expression in the hippocampal CA1 region of CRS mice. Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3β, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice. These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3β and Erk1/2 signaling pathways. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/25869780/Flupirtine_attenuates_chronic_restraint_stress_induced_cognitive_deficits_and_hippocampal_apoptosis_in_male_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(15)00246-6 DB - PRIME DP - Unbound Medicine ER -