Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder

Abstract

Neuroimaging and postmortem studies of subjects with major depressive disorder (MDD) reveal smaller hippocampal volume with lengthening duration of illness. Pathology in astrocytes may contribute significantly to this reduced volume and to the involvement of the hippocampus in MDD. Postmortem hippocampal tissues were collected from 17 subjects with major depressive disorder and 17 psychiatrically-normal control subjects. Sections from the body of the hippocampus were immunostained for glial fibrillary acidic protein (GFAP), a marker of intermediate filament protein expressed in astrocytes. The density of GFAP-immunoreactive astrocytes was measured in the hippocampus using 3-dimensional cell counting. Hippocampal subfields were also assessed for GFAP-immunoreactive area fraction. In CA1, there was a significant positive correlation between age and either density or area fraction in MDD. The density of astrocytes in the hilus, but not CA1 or CA2/3, was significantly decreased only in depressed subjects not taking an antidepressant drug, but not for depressed subjects taking an antidepressant drug. The area fraction of GFAP-immunoreactivity was significantly decreased in the dentate gyrus in women but not men with depression. In CA2/3, the area fraction of GFAP-immunoreactivity was inversely correlated with the duration of depression in suicide victims. Astrocyte contributions to neuronal function in the hilus may be compromised in depressed subjects not taking antidepressant medication. Due to the cross-sectional nature of the present study of postmortem brain tissue, it remains to be determined whether antidepressant drug treatment prevented a decrease in GFAP-immunoreactive astrocyte density or restored cell density to normal levels.

Human-specific features of spatial gene expression and regulation in eight brain regions

“…Astrocytes were further shown to contribute to the integration of adult-born neurons in the hippocampus, although adult hippocampal neurogenesis in humans remains controversial (Krzisch et al 2015;Sultan et al 2015;Sorrells et al 2018). Moreover, the involvement of hippocampal astrocytes and astrocyte-neuron interactions in Huntington's disease, major depressive disorder, and schizophrenia have been reported (Kolomeets and Uranova 2010;Cobb et al 2016;L'Episcopo et al 2016). …”

Stress and Loss of Adult Neurogenesis Differentially Reduce Hippocampal Volume

“…Several other known effects of stress, including decreased numbers of inhibitory interneurons throughout the hippocampus (68), decreased numbers of glia in the neuropil (69), and decreased hippocampal microvasculature (70) are potential factors. Glial cells, particularly astrocytes, are reduced in number and size in both human depression and animal models of chronic stress (71–73), suggesting a potential contribution to volume change.…”

Tissue Type-Specific Bioenergetic Abnormalities in Adults with Major Depression

“…Post-mortem brain studies have consistently shown that the most important cellular abnormality in MDD is represented by reductions in glial cells and specifically in astrocytes, rather than neurons (Cobb et al, 2016;Ongur et al, 1998;Rajkowska and Stockmeier, 2013). Astrocytes (and especially protoplasmic astrocytes present in the gray matter) have a crucial role in regulating several energy-intensive processes involving neurons, including glucose metabolism, neurotransmitter uptake (particularly glutamate and the cycling from glutamate-glutamine), synaptic development and maturation, and the blood-brain barrier (Kettenmann and Ranson, 2005).…”