共 45 条
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.
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页码:106 / 110
页数:5
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