Glia in the Locus Coeruleus in Major Depression and Suicide

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Recent postmortem studies have demonstrated deficits in glia in major depressive disorder, including reductions in the astrocyte specific interfilament glial fibrillary acidic protein (GFAP) in the prefrontal cortex and cerebellum of depressed patients. Astrocytes serve important roles in influencing neuronal activity in the CNS, one of which is to remove neurotransmitters from the extracellular space. The present study investigated the levels of GFAP in the locus coeruleus (LC) of human subjects. The LC is the principal source of norepinephrine in the brain and neurochemical pathology of the LC has been demonstrated in major depressive disorder (MDD) and suicide. Tissue punches of the LC were obtained from postmortem brains collected from subjects with MDD who died by suicide and psychiatrically normal control subjects (n=9 per group). The age of the subjects ranged from 17 to 65 years (control 37±4 y; MDD 39±5 y) and postmortem intervals ranged from 17 to 44 h (control 20±1 h; MDD 25±3 h). GFAP-immunoreactivity (ir) was measured by quantitative Western blotting. Alpha-tubulin-ir was used to control for protein loading and transfer. Amounts of GFAP-ir were highly variable within both control and MDD subjects, ranging 15-fold across control subjects and 24-fold across MDD subjects. There was a modest trend for lower GFAP-ir in the LC from MDD subjects relative to control subjects, but this difference was not significantly different. In control subjects, there was no significant correlation of GFAP-ir levels with age. In contrast, GFAP-ir levels were positively correlated with age in MDD subjects. In younger MDD subjects (<40 y), GFAP-ir was consistently lower as compared to matched control subjects. Amounts of GFAP-ir did not correlate with postmortem intervals. These findings are consistent with a previous report demonstrating age effects on GFAP in frontal cortex in depressed but not control subjects. Glia deficits reported in frontal cortex and cerebellum from depressed subjects may also occur in the brainstem, and these deficits may contribute to disruption of monoamine chemistry in depression. Given the variability of GFAP levels in the LC between subjects, other markers of glia should be pursued to evaluate the potential role of glia in brainstem pathology associated with MDD.

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