In the present study, to define the roles of nitric oxide (NO) signaling in amyloid-β (Aβ) production after transient cerebral ischemia, extracellular levels of NO and Aβ 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 Aβ levels. In addition, the NO elevation preceded the Aβ changes. The Western blotting suggested that acute hypoperfusion could increase the expression of β-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 Aβ changes and rescue the delayed neuronal death. These preliminary findings indicated that activation of NOS/NO signaling system could trigger Aβ 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 Aβ production and neuronal damage induced by transient cerebral ischemia.
- Amyloid β
- Nitric oxide