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Study Sheds Light on Astrocyte Disruption in Depression

A new study published by the team of Naguib Mechawar, Ph.D., a researcher with the McGill Group for Suicide Studies (MGSS) of the Douglas Institute (CIUSSS de l’Ouest-de-l’Ile de Montreal) and associate professor in the Department of Psychiatry at McGill University, sheds new light on the disruption of astrocytes in depression. Astrocytes, a class of non-neuronal cells, have previously been implicated in depression and suicide.

However, it was not known whether these cells were affected throughout the brain or only in certain regions. This research provides evidence that networks of astrocytes are altered specifically in areas of the brain associated with mood regulation. In addition, in describing the existence of new subtypes of astrocyte, this study reveals features specific to the human brain. The diversity and functional and morphological complexity of cortical astrocytes in humans, as well as their involvement in normal and pathological brain function, have only recently begun to be recognized. In particular, accumulating data generated by the MGSS and other independent research groups have indicated an abnormal regulation of astrocytic genes in the prefrontal cortex of patients who died while suffering from depression.

Breaking new ground

This is an astrocyte, labeled with GFAP (red), Focal Adhesion Kinase (FAK) green, and nuclear stain To-Pro (blue).

This research provides evidence that networks of astrocytes are altered specifically in areas of the brain associated with mood regulation. The image is for illustrative purposes only. Image credit: Nathan S. Ivey at TNPRC.

This work, carried out by MGSS doctoral candidates Susana Gabriela Torres-Platas and Corina Nagy, breaks new ground. Based on the analysis of postmortem brain samples from the Douglas-Bell Canada Brain Bank, it demonstrates that the expression of the astrocyte-specific marker GFAP, which is significantly decreased in the prefrontal cortex of depressed suicides compared to that of healthy controls, is normal in other cortical areas that are not traditionally associated with depression, such as the visual cortex. However, GFAP expression was also found to be decreased in subcortical brain regions that are interconnected to the prefrontal cortex or that were previously implicated in mood disorders. ‘Within these subcortical regions, in samples from both patients and healthy individuals, we also observed astrocytes that were larger and more complex than those seen in cortical areas. We are currently analyzing these cells to better understand their unique properties in the human brain. I am convinced that it is important to describe how the human brain is organized at the microscopic level, and how this organization is altered in depression, in order to better understand the biological causes of this illness. This should help develop new therapeutical targets,’ explains Mechawar. This study appears today in the journal Molecular Psychiatry.

About this psychology research

Funding: This work was funded by the Canadian Institutes of Health Research (CIHR) and the Fonds de recherche du Quebec-Sante (ERANET-NEURON).

Source: Florence Meney – Douglas Mental Health University Institute
Image Source: Image is credited to Nathan S. Ivey at TNPRC, and is licensed Creative Commons Attribution 3.0 Unported
Original Research: Abstract for “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” by S G Torres-Platas, C Nagy, M Wakid, G Turecki and N Mechawar in Molecular Psychiatry. Published online June 2 2015 doi:10.1038/mp.2015.65


Abstract

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

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.

“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” by S G Torres-Platas, C Nagy, M Wakid, G Turecki and N Mechawar in Molecular Psychiatry. Published online June 2 2015 doi:10.1038/mp.2015.65

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