期刊
JOURNAL OF NEUROCHEMISTRY
卷 91, 期 5, 页码 1057-1066出版社
WILEY
DOI: 10.1111/j.1471-4159.2004.02792.x
关键词
cerebellum; locus coeruleus; major depression; neuronal nitric oxide synthase
资金
- NCRR NIH HHS [P20 RR017701-039009, P20 RR017701-037882, P20 RR017701, RR17701] Funding Source: Medline
- NIMH NIH HHS [K02 MH002031, R01 MH046692, R01 MH063187, MH46692, R01 MH063187-03, MH/AG02031, R01 MH046692-11, MH63187, K02 MH002031-03] Funding Source: Medline
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.
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