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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

Molecular Psychiatry volume 21, pages 509–515 (2016)Cite this article

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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.

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Acknowledgements

We thank Quebec's Coroner office as well as the next-of-kin of the deceased for their support. We also thank the expert staff of the Douglas-Bell Canada Brain Bank (Maâmar Bouchouka, Josée Prud'homme, Danielle Cécyre, and Lucie Ratelle). This work has been funded by operating grants to NM from CIHR (grant number MOP-111022) and ERANET-NEURON, as well as an infrastructure grant to NM from CFI and an equipment grant to NM from NSERC. NM is the Bell Senior Fellow in Mental Health, as well as a FRQS chercheur-boursier Junior 2 and CIHR New Investigator. SGTP is the recipient of a CONACyT doctoral scholarship and CN is the recipient of FRQS doctoral scholarship.

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Author notes

  1. S G Torres-Platas and C Nagy: These authors contributed equally to this work.

Authors and Affiliations

  1. McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC, Canada

    S G Torres-Platas, C Nagy, M Wakid, G Turecki & N Mechawar

  2. Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada

    S G Torres-Platas, C Nagy & N Mechawar

  3. Department of Human Genetics, McGill University, Montreal, QC, Canada

    G Turecki

  4. Department of Psychiatry, McGill University, Montreal, QC, Canada

    G Turecki & N Mechawar

Authors
  1. S G Torres-Platas
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  2. C Nagy
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  3. M Wakid
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  4. G Turecki
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  5. N Mechawar
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Correspondence to N Mechawar.

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Torres-Platas, S., Nagy, C., Wakid, M. et al. 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. Mol Psychiatry 21, 509–515 (2016). https://doi.org/10.1038/mp.2015.65

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