Karolewicz B, Szebeni K, Stockmeier C A, Konick L, Overholser J C, Jurjus G, Roth B L, Ordway G A
Department of Psychiatry & Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
J Neurochem. 2004 Dec;91(5):1057-66. doi: 10.1111/j.1471-4159.2004.02792.x.
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.
谷氨酸能和去甲肾上腺素能信号传导的中断被认为发生在抑郁症中。谷氨酸为去甲肾上腺素能蓝斑（LC）提供兴奋性输入。在本研究中，在正常人类LC中检测了针对神经元型一氧化氮合酶（nNOS）的免疫反应性的位置，nNOS是谷氨酸受体激活的细胞内介质，并评估了重度抑郁症中可能发生的nNOS免疫反应性的潜在变化。从11至12对匹配的重度抑郁症患者和无重大精神疾病诊断的对照受试者中获取含有LC以及非边缘性LC投射区域（小脑）的组织。在LC区域，在含大量神经黑色素的神经元、缺乏神经黑色素的小神经元和胶质细胞中发现了nNOS免疫反应性。与对照受试者相比，抑郁症患者LC中的nNOS免疫反应性水平显著降低（-44%，p<0.05），但小脑中没有。在两个脑区中，抑郁症患者而非对照受试者的nNOS水平与脑pH值呈正相关。LC中低水平的nNOS可能反映了重度抑郁症中该核团兴奋性输入的改变。然而，pH似乎影响抑郁症患者nNOS免疫反应性的保存。这一因素可能部分导致了抑郁症中nNOS水平较低。
