Effect of ?-amyloid_(1-40) on the expression of nitric oxide synthase in rat brain / 中华神经科杂志

ABSTRACT

Objective To investigate the role of nitric oxide synthase (NOS) in neurotoxic mechanisms of beta amyloid (A?) and the pathogenesis of Alzheimer′s disease (AD). Methods 35 adult rats were divided into 3 groups normal control,saline injection,and A? 1 40 injection groups A? 1 40 was initially solubilized in saline (10?g/?l) and incubated for at least 1 week before use 1?l incubated A? 1 40 or saline were injected into dorsal blade of dentate gyrus in right hippocampus of rats Immunohistochemical assay of neuronal NOS (nNOS) and inducible NOS (iNOS) was performed at the 2 nd,10 th,and 30 th day after A? 1 40 or saline injection. Results The nNOS like immunoreactivity (nNOSLIR) neurons were found in different brain regions such as cortex,striatum and hippocampus of normal rats,and the number of neurons in dentate gyrus was 8 96?0 31 The number and configuration of nNOSLIR neurons were found without changes after saline injection (8 97?0 29) At 2,10,and 30 d after A? 1 40 injection,the number of nNOS neurons at the site around injection was significantly reduced (3 13?0 27,2 89?0 19 and 2 91?0 25 respectively),but there were no notable differences at these three experimental time points iNOS like immunoreactivity (iNOSLIR) cells were not found in any brain region of normal or saline injected rats After A? 1 40 injection,a large percentage of glia (mainly were astrocytes) had an activated morphological change and showed a strong iNOSLIR around the injection site The responded areas with these cells were 0 905?0 082,0 962?0 161 and 0 935?0 125 mm 2 respectively at 2,10 and 30 day after A? 1 40 injection,but there appeared no significant differences among them. Conclusions The results demonstrate that intrahippocampal injection of A? 1 40 may result in a significant loss of nNOS neurons and induce a considerable expression of iNOS in astrocytes,indicating that NOS may play an important role in neurotoxic mechanisms of A? and the pathogenesis of AD