Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke

• Published in: Journal of neuroscience research 2009-01, Vol.87 (1), p.112-122
• Main Authors: Li, Wen-Lei, Cai, Hui-Hui, Wang, Bin, Chen, Ling, Zhou, Qi-Gang, Luo, Chun-Xia, Liu, Na, Ding, Xin-Sheng, Zhu, Dong-Ya
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Antimetabolites - pharmacology; Bromodeoxyuridine - metabolism; Cell Count - methods; Cognition Disorders - diagnosis; Cognition Disorders - drug therapy; Cognition Disorders - pathology; Disease Models, Animal; fluoxetine; Fluoxetine - therapeutic use; focal cerebral ischemia; hippocampus; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - drug therapy; Male; Maze Learning - drug effects; Mice; Mice, Inbred C57BL; neurogenesis; Neurogenesis - drug effects; Neurons - drug effects; Neurons - physiology; Psychomotor Performance - drug effects; Reaction Time - drug effects; sensorimotor function; Serotonin Uptake Inhibitors - therapeutic use; Severity of Illness Index; Space Perception - drug effects; spatial cognitive function; Swimming; Time Factors; Zidovudine - pharmacology
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.21829

Cognitive deficits, including spatial memory impairment, are very common after ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming spatial memory in the ischemic brain. Fluoxetine, a selective serotonin reuptake inhibitor, can enhance neurogenesis in the hippocampus in physiological situations and some neurological diseases. However, whether it has effects on ischemia‐induced spatial cognitive impairment and hippocampal neurogenesis has not been determined. Here we report that fluoxetine treatment (10 mg kg−1, i.p.) for 4 weeks promoted the survival of newborn cells in the ischemic hippocampus and, consequently, attenuated spatial memory impairment of mice after focal cerebral ischemia. Disrupting hippocampal neurogenesis blocked the beneficial effect of fluoxetine on ischemia‐induced spatial cognitive impairment. These results suggest that chronic fluoxetine treatment benefits spatial cognitive function recovery following ischemic insult, and the improved cognitive function is associated with enhanced newborn cell survival in the hippocampus. Our results raise the possibility that fluoxetine can be used as a drug to treat poststroke spatial cognitive deficits. © 2008 Wiley‐Liss, Inc.