Possible involvement of NO/NOS signaling in hippocampal amyloid-β production induced by transient focal cerebral ischemia in aged rats

被引:23
作者
Li, Song [1 ]
Wang, Wei [1 ,2 ]
Wang, Che [3 ]
Tang, Yi-Yuan [1 ]
机构
[1] Dalian Univ Technol, Inst Neuroinformat, Dalian 116024, Peoples R China
[2] Dalian Univ Technol, Affiliated Zhongshan Hosp, Dalian 116001, Peoples R China
[3] Liaoning Normal Univ, Coll Chem & Chem Engn, Dept Pharm, Dalian 116029, Peoples R China
关键词
Nitric oxide; Amyloid beta; Ischemia; Hippocampus; BACE1; L-NAME; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; ARTERY OCCLUSION; GAMMA-SECRETASE; UP-REGULATION; BRAIN; EXPRESSION; STRESS; INJURY;
D O I
10.1016/j.neulet.2009.12.064
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the present study, to define the roles of nitric oxide (NO) signaling in amyloid-beta (A beta) production after transient cerebral ischemia, extracellular levels of NO and A beta were monitored by intracerebral microdialysis in the hippocampus of aged rats exposed to transient middle cerebral artery occlusion and reperfusion (MCAO/R). The results indicated that 1-h MCAO significantly upregulated hippocampal NO and A beta levels. in addition, the NO elevation preceded the A beta changes. The Western blotting suggested that acute hypoperfusion could increase the expression of beta-secretase 1 (BACE1) but not BACE2. The enhanced NO concentration in acute stage of MCAO/R was coincident with increased eNOS expression, while in subacute stage was coincident with increased iNOS and nNOS. Our results also indicated that pretreatment of L-NAME, one non-selective NOS inhibitor could decrease the BACE1 expression, reverse both NO and A beta changes and rescue the delayed neuronal death. These preliminary findings indicated that activation of NOS/NO signaling system could trigger A beta production through BACE1 pathway during acute ischemic episode. The present data may be important in understanding, at least in part, the pathological role of NO/NOS system involved in hippocampal A beta production and neuronal damage induced by transient cerebral ischemia. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:106 / 110
页数:5
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