Age-Dependent Reductions in the Level of Glial Fibrillary Acidic Protein in the Prefrontal Cortex in Major Depression

Abstract

The density of glial cells is reduced in certain layers of the dorsolateral prefrontal cortex in major depressive disorder (MDD). Moreover, there are reductions in the packing density of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes in the same cortical layers in younger subjects with MDD. The objective of the present study was to test if the level of GFAP is preferentially decreased in younger subjects with MDD, and whether GFAP levels are correlated with the age of onset of depression. Post-mortem brain tissue punches from dorsolateral prefrontal cortex were collected from 15 subjects with MDD and 15 age-matched psychiatrically normal control subjects. Western blots were performed on gels containing duplicated samples from both subjects of each matched pair, and on gels containing samples at different ages from either the MDD or the control group. The GFAP level was calculated as the ratio of the optical density of GFAP bands to actin bands in subjects with MDD and nonpsychiatric controls. Levels of GFAP were significantly lower in subjects with MDD as compared to controls and this decrease was most prominent in subjects less than 60 years old at the time of death. In the MDD group, GFAP levels were positively correlated with age at the time of death and show a trend toward correlation with the age of onset of depression. These findings indicate that a decrease in levels of GFAP may contribute to the pathophysiology of MDD, particularly in subjects of relatively young age.

Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder

“…In addition, we found reduced density of GFAP-immunostained astrocytes in the LC region in the MDD samples compared with matched control samples. Reduced GFAP immunoreactivity in MDD has been reported for anterior cingulate cortex white matter, 42 dorsolateral prefrontal cortex deep layers, 43,44 the amygdala 16 and the cerebellum. 45 Interestingly, Wistar-Kyoto rats (a strain often used as a model of depression and stress sensitivity) exhibit lower levels of GFAP immunoreactivity in the cerebral cortex and amygdala and a reduced number of GFAPimmunoreactive astrocytes compared with Sprague-Dawley rats.…”

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

“…[170][171][172][173][174] Although some reports did not differentiate between the loss of microglial cells or astrocytes, this difference is crucial due to the different effects of the type 1/type 2 immune response. Recent studies show that in particular astrocytes are diminished in MD, [175][176][177] although the data are not fully consistent. 178 A loss of astrocytes was particularly observed in younger depressed patients: the lack of glial fibrillary acidic acid (GFAP)-immunoreactive astrocytes reflects a lowered activity of responsiveness in those cells.…”

Repeated Unpredictable Stress and Antidepressants Differentially Regulate Expression of the Bcl-2 Family of Apoptotic Genes in Rat Cortical, Hippocampal, and Limbic Brain Structures

“…Previous work has shown that exposure to 21 days of restraint stress in rats decreased the length and number of branch points of dendrites in the anterior Cg and prelimbic cortices (Radley et al, 2004). Neuroimaging and postmortem studies have clearly demonstrated reductions in frontal lobe volumes and decreases in cell number and/ size in anterior Cg, dorsolateral, prefrontal, subgenual, and orbitofrontal cortices (Rajkowska, 2000;Si et al, 2004). The higher cognitive areas of the anterior Cg, Fr cortices, and CeA where we observed regulation of Bcl-2 correspond well with regions where volumetric and structural impairments are observed in patients with depression.…”