Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder
J A Cobb1, K O'Neill1, J Milner1
1Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA.
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 MDD 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.
Insights
Major depressive disorder (MDD) is linked to smaller hippocampal volumes. This study found reduced glial fibrillary acidic protein (GFAP) in astrocytes within specific hippocampal areas, particularly in depressed individuals not on medication.
Area of Science:
- Neuroscience
- Pathology
- Cell Biology
Background:
- Major depressive disorder (MDD) is associated with reduced hippocampal volume, with duration of illness correlating with this change.
- Astrocytic pathology is hypothesized to contribute to hippocampal volume reduction in MDD.
Purpose of the Study:
- To investigate the density and GFAP-immunoreactive area fraction of astrocytes in the hippocampus of subjects with MDD compared to controls.
- To explore correlations between astrocytic markers, illness duration, age, sex, and antidepressant treatment in MDD.
Main Methods:
- Postmortem hippocampal tissues from 17 MDD subjects and 17 controls were analyzed.
- Immunohistochemistry for glial fibrillary acidic protein (GFAP) was performed.
- 3D cell counting and area fraction analysis were used to quantify astrocytes in hippocampal subfields.
Main Results:
- A significant positive correlation between age and GFAP density/area fraction was observed in the CA1 subfield of MDD subjects.
- Decreased astrocyte density in the hilus was found in MDD subjects not taking antidepressants.
- Reduced GFAP area fraction in the dentate gyrus was observed in female MDD subjects.
- In suicide victims, CA2/3 GFAP area fraction inversely correlated with depression duration.
Conclusions:
- Astrocytic alterations, indicated by GFAP changes, are present in the hippocampus in MDD, varying by subfield, sex, and medication status.
- Compromised astrocyte-neuron interactions in the hilus may occur in untreated MDD.
- Further research is needed to determine if antidepressant treatment affects astrocyte density.
