Widespread Decrease of Cerebral Vimentin-Immunoreactive Astrocytes in Depressed Suicides

Abstract

Post-mortem investigations have implicated cerebral astrocytes immunoreactive (-IR) for glial fibrillary acidic protein (GFAP) in the etiopathology of depression and suicide. However, it remains unclear whether astrocytic subpopulations IR for other astrocytic markers are similarly affected. Astrocytes IR to vimentin (VIM) display different regional densities than GFAP-IR astrocytes in the healthy brain, and so may be differently altered in depression and suicide. To investigate this, we compared the densities of GFAP-IR astrocytes and VIM-IR astrocytes in post-mortem brain samples from depressed suicides and matched non-psychiatric controls in three brain regions (dorsomedial prefrontal cortex, dorsal caudate nucleus and mediodorsal thalamus). A quantitative comparison of the fine morphology of VIM-IR astrocytes was also performed in the same regions and subjects. Finally, given the close association between astrocytes and blood vessels, we also assessed densities of CD31-IR blood vessels. Like for GFAP-IR astrocytes, VIM-IR astrocyte densities were found to be globally reduced in depressed suicides relative to controls. By contrast, CD31-IR blood vessel density and VIM-IR astrocyte morphometric features in these regions were similar between groups, except in prefrontal white matter, in which vascularization was increased and astrocytes displayed fewer primary processes. By revealing a widespread reduction of cerebral VIM-IR astrocytes in cases vs. controls, these findings further implicate astrocytic dysfunctions in depression and suicide.

Keywords: GFAP; astrocyte; depression; human; post-mortem; suicide; vimentin.

Figure 1

Lower densities of GFAP-IR cerebral astrocytes in depressed suicides relative to controls. (A) Representative micrographs illustrating GFAP-IR astrocytes in the prefrontal cortex gray matter (PFC GM). Scale bars = 50 μm. (B–E) Depressed suicides had significantly lower densities of GFAP-IR astrocytes than controls in all regions examined except in the prefrontal cortex white matter (PFC WM), in which the difference was nearly significant. *p ≤ 0.05; n = 10; unpaired t-tests corrected for age, pH and post-mortem interval.

Figure 2

Lower densities of VIM-IR cerebral astrocytes in depressed suicides relative to controls. (A) Representative micrographs illustrating VIM-IR astrocytes in the caudate nucleus. Scale bars = 50 μm. (B–E) Depressed suicides had significantly lower densities of GFAP-IR astrocytes than controls in the caudate nucleus, the prefrontal cortex gray matter (PFC GM) and the prefrontal cortex white matter (PFC WM). No group difference was observed in the mediodorsal thalamus, which presented exceedingly few VIM-IR astrocytes in both groups. *p ≤ 0.05; n = 10; unpaired t-tests corrected for age, pH and post-mortem interval.

Figure 3

VIM-IR astrocyte morphology is generally similar in depressed suicides vs. controls. (A) 3D reconstruction of a VIM-IR astrocyte from the prefrontal cortex white matter (PFC WM) representative of those from depressed suicides (left). The soma (pink) that extends primary processes (green) which can branch at nodes (yellow) into secondary processes (red) that eventually end as terminals (blue). Branched Structure Analysis (BSA) measurements have been annotated (left), and a minimum intensity projection of a representative VIM-IR astrocyte from the caudate nucleus of a depressed suicide is illustrated (right). (B–I) The BSA revealed a lower (primary) process number for VIM-IR astrocytes in the PFC WM of depressed suicides relative to controls. There were no group differences for any BSA measurements of VIM-IR astrocytes in the prefrontal cortex gray matter (PFC GM), thalamus or caudate nucleus. *p ≤ 0.05; n = 10; unpaired t-tests corrected for age, pH and post-mortem interval.

Figure 4

Increased CD31-IR vascular density in cortical white matter from depressed suicides relative to controls. (A) Representative micrographs showing that CD31-IR vascular density in the prefrontal cortex white matter (PFC WM). Scale bars = 50 μm. (B–E) Depressed suicides had a significantly higher vascular density than controls in the mediodorsal thalamus. No group differences were observed in the prefrontal cortex gray matter (PFC GM), the caudate nucleus or the mediodorsal thalamus. *p ≤ 0.05; n = 10; unpaired t-tests corrected for age, pH and post-mortem interval.

Figure 5

Visual representation of astrocyte densities in depressed suicides. Each cube represents 1 mm³ of cerebral tissue in which are distributed the stereological estimates of cell densities reported in Figures 1, 2 (cell body diameter = 25 μm). These illustrations demonstrate that astrocyte density is greatly and widely affected in depressed suicides relative to controls.