Reduced expression of NO-sensitive guanylyl cyclase in reactive astrocytes of Alzheimer disease, Creutzfeldt-Jakob disease, and multiple sclerosis brains
Reduced expression of NO-sensitive guanylyl cyclase in reactive astrocytes of Alzheimer disease, Creutzfeldt-Jakob disease, and multiple sclerosis brains
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DOI：
10.1016/j.nbd.2004.07.022
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发表时间：
2004-12-01
影响因子：
6.1
通讯作者：
García, A
中科院分区：
文献类型：
--
作者：
Baltrons, MA;Pifarré, P;García, A
在阿尔茨海默病（AD）中，在淀粉样斑块周围的反应性星形胶质细胞中发现了增加的NO合酶（NOS）表达。我们最近发现，在培养的星形胶质细胞和成年大鼠脑中，用P-淀粉样肽或IL-1 β治疗可下调NO敏感的可溶性鸟苷酸环化酶（sGC）。在这项工作中，我们研究了sGC的活性和表达在AD患者和匹配的对照死后的脑组织。在基础或NO刺激的sGC活性，也没有观察到显着的改变，也在sGC β 1和α 1亚基水平的AD大脑皮质提取物。免疫组化显示sGC 1在皮质和海马神经元以及白色物质纤维状星形胶质细胞中强烈和广泛的标记，而灰质星形胶质细胞染色微弱。在AD中，sGC在神经元和纤维状星形胶质细胞中的表达没有改变，但在淀粉样斑块周围的反应性星形胶质细胞中显著减少。在Creutzfeldt-Jakob病脑的皮质和皮质下白色物质中以及在多发性硬化（MS）脑的亚急性和慢性斑块中，sGC 31的免疫染色也缺乏。因此，星形胶质细胞反应性的诱导与体外和体内响应于NO产生cGMP的能力降低有关。这种作用可能与星形胶质细胞炎症反应的发展有关。(C)2004年爱思唯尔公司All rights reserved.
In Alzheimer's disease (AD) brains increased NO synthase (NOS) expression is found in reactive astrocytes surrounding amyloid plaques. We have recently shown that treatment with P-amyloid peptides or IL-1beta down-regulates NO-sensitive soluble guanylyl cyclase (sGC) in cultured astrocytes and in adult rat brain. In this work, we have examined sGC activity and expression in postmortem brain tissue of AD patients and matched controls. No significant alteration was observed in basal or NO-stimulated sGC activity, nor in sGC beta1 and alpha1 subunit levels in cortical extracts of AD brains. Immunohistochemistry showed intense and widespread labeling of sGC l in cortical and hippocampal neurons and white matter fibrillar astrocytes, while grey matter astrocytes were faintly stained. In AD, expression of sGC in neurons and fibrillar astrocytes is not altered but is markedly reduced in reactive astrocytes surrounding amyloid plaques. Immunostaining for sGC 31 was also lacking in reactive astrocytes in cortex and subcortical white matter in Creutzfeldt-Jakob disease brains and in subacute and chronic plaques in multiple sclerosis (MS) brains. Thus, induction of astrocyte reactivity is associated with decreased capacity to generate cGMP in response to NO both in vitro and in vivo. This effect may be related to the development of the astroglial inflammatory response. (C) 2004 Elsevier Inc. All rights reserved.