Low nNOS protein in the locus coeruleus in major depression
Low nNOS protein in the locus coeruleus in major depression
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DOI：
10.1111/j.1471-4159.2004.02792.x
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发表时间：
2004-12-01
影响因子：
4.7
通讯作者：
Ordway, GA
中科院分区：
文献类型：
--
作者：
Karolewicz, B;Szebeni, K;Ordway, GA
谷氨酸和去甲肾上腺素能信号的中断被认为发生在抑郁障碍中。谷氨酸为去甲肾上腺素能蓝斑(LC)提供兴奋性输入。本研究对谷氨酸受体激活的细胞内介质神经元型一氧化氮合酶(NNOS)免疫反应在正常人LC中的定位进行了研究，并对nNOS免疫反应在抑郁症中可能发生的变化进行了评估。包含LC的组织和非边缘LC投影区(小脑)是从11到12对匹配的重度抑郁症患者和没有主要精神疾病诊断的对照组中获得的。在LC区，含神经黑色素的大神经元、缺少黑色素的小神经元和神经胶质细胞均有nNOS免疫反应阳性。与对照组相比，抑郁症患者小脑中nNOS免疫反应水平显著降低(-44%，p<；0.05)。在抑郁的受试者中，nNOS水平与大脑的pH值呈正相关，而在对照组中，这两个脑区的nNOS水平与脑pH值呈正相关。LC中nNOS的低水平可能反映了重度抑郁症患者对该核团兴奋性输入的改变。然而，在抑郁症患者中，pH似乎会影响nNOS免疫反应性的保存。这一因素可能在一定程度上导致抑郁症患者nNOS水平较低。
Disruptions of glutamatergic and noradrenergic signaling have been postulated to occur in depressive disorders. Glutamate provides excitatory input to the noradrenergic locus coeruleus (LC). In this study, the location of immunoreactivity against neuronal nitric oxide synthase (nNOS), an intracellular mediator of glutamate receptor activation, was examined in the normal human LC, and potential changes in nNOS immunoreactivity that might occur in major depression were evaluated. Tissue containing LC, and a non-limbic, LC projection area (cerebellum) was obtained from 11 to 12 matched pairs of subjects with major depression and control subjects lacking major psychiatric diagnoses. In the LC region, nNOS immunoreactivity was found in large neuromelanin-containing neurons, small neurons lacking neuromelanin, and glial cells. Levels of nNOS immunoreactivity were significantly lower in the LC (-44%, p < 0.05), but not in the cerebellum, when comparing depressed with control subjects. nNOS levels were positively correlated with brain pH values in depressed, but not control, subjects in both brain regions. Low levels of nNOS in the LC may reflect altered excitatory input to this nucleus in major depression. However, pH appears to effect preservation of nNOS immunoreactivity in subjects with depression. This factor may contribute, in part, to low levels of nNOS in depression.