Fluoxetine ameliorates cognitive impairments induced by chronic cerebral hypoperfusion via down-regulation of HCN2 surface expression in the hippocampal CA1 area

出 版 物：《中国药理学通报》 (Chinese Pharmacological Bulletin)

年 卷 期：2015年第31卷第B11期

页      面：78-78页

核心收录：

学科分类：10[医学] 

主　　题：fluoxetine chronic cerebral hypoperfusion cognitive impairments HCN2 subunit hippocampal CA1area rats 

摘      要：Aim To investigate whether tluoxetine, a selective serotonin reuptake inhibitor（ SSRI） , could amelio- rate cognitive impairments induced by chronic cerebral hypopeffusion in rats and to clarify the underlying mecha- nisms of its efficacy. Methods Rats were subjected to permanent bilateral occlusion of the common carotid arteries （two-vessel occlusion, 2VO）. Two weeks later, rats were treated with 30 mg · kg^-1 fluoxetine （intragastric injec- tion, i. g. ） for 6 weeks. Cognitive function was evaluated by Morris water maze （MWM） and novel objects recog- nition （NOR） test. Long-term potentiation （LTP） was used to address the underlying synaptic mechanisms. West- ern blot was used to quantify the protein levels. Results Fluoxetine treatment significantly improved the cognitive 2VO impairments caused by 2VO, accompanied with a reversion of 2VO-induced inhibitory of LTP. Furthermore, caused an up-regulation of hyperpolarization-activated cyclic nueleotide-gated channel 2 （HCN2） surface expres- sions in the hippocampal CA1 area and fluoxetine also effectively recovered the up-regulation of HCN2 surface ex- pressions. Conclusion Fluoxetine can ameliorate cognitive impairments induced by chronic cerebral hypopeffusion and a possible mechanism may via down-regulating HCN2 surface expression in the Hippocampal CA1 area.