Glial fibrillary acidic protein is differentially expressed across cortical and subcortical regions in healthy brains and downregulated in the thalamus and caudate nucleus of depressed suicides

Abstract

There is mounting evidence to suggest aberrant astrocytic function in depression and suicide. Independent studies have reported astrocytic abnormalities in certain brain regions, but it remains unclear whether this is a brain-wide phenomenon. The present study examined this question by measuring glial fibrillary acidic protein (GFAP) expression in postmortem brain samples from suicide completers and matched non-psychiatric controls. Suicide completers were selected based on their recent characterization as low GFAP expressors in the prefrontal cortex, (Brodmann areas 8/9 and 10). Real-time PCR and immunoblotting were used to measure GFAP gene expression and protein levels in BA4 (primary motor cortex), BA17 (primary visual cortex), cerebellar cortex, mediodorsal thalamus and caudate nucleus. We found downregulation of GFAP mRNA and protein in the mediodorsal thalamus and caudate nucleus of depressed suicides compared with controls, whereas GFAP expression in other brain regions was similar between groups. Furthermore, a regional comparison including all samples revealed that GFAP expression in both subcortical regions was, on average, between 11- and 15-fold greater than in cerebellum and neocortex. Examining astrocyte morphology by immunohistochemistry showed that astrocytes in both thalamus and caudate displayed larger cell bodies and extended more ramified processes across larger domains than the previously described cortical astrocytes. This study reveals that astrocytic abnormalities are not brain wide and suggests that they are restricted to cortical and subcortical networks known to be affected in mood disorders. Additionally, our results show a greater diversity in human astrocytic phenotypes than previously thought.