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bioRxiv · 10.1101/2021.09.22.461367

Assessing the relationships between neurological and psychiatric diseases with astrocyte subtypes and psychotropic medications

Zhang, X.·Wolfinger, A. M.·Shukla, R. M.·Lundh, A. E.·Wu, X.·Abel, M.·McCullumsmith, R. E.·O'Donovan, S. M.
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Abstract

Astrocytes have many important functions in the brain, but their roles in CNS disorders and their responses to psychotropic medications are still being elucidated. In this study, we used gene enrichment analysis to assess the relationships between different astrocyte subtypes, neurological and psychiatric diseases, and psychotropic medications. We also carried out qPCR analyses and "look-up" studies to further assess the chronic effects of these drugs on astrocyte marker gene expression. Our bioinformatic analysis identified differential gene enrichment of different astrocyte subtypes in CNS disorders. The "common" astrocyte subtype was the most frequently enriched across disorders, but the highest level of enrichment was found in depression, supporting a role for astrocytes in this disorder. We also identified common enrichment of metabolic and signal transduction-related biological processes in astrocyte subtypes and CNS disorders. However, enrichment of different psychotropic medications, including antipsychotics, antidepressants, and mood stabilizers, was limited in astrocyte subtypes. These results were confirmed by "look-up" studies and qPCR analysis, which also reported little effect of common psychotropic medications on astrocyte marker gene expression, suggesting that astrocytes are not a primary target of these medications. Overall, this study provides a unique view of astrocyte subtypes and the effect of medications on astrocytes in disease, which will contribute to our understanding of their role in CNS disorders and offers insights into targeting astrocytes therapeutically.

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Zhang, X., Wolfinger, A. M., Shukla, R. M., Lundh, A. E., Wu, X., Abel, M., McCullumsmith, R. E., O'Donovan, S. M.. 2021-09-24. Assessing the relationships between neurological and psychiatric diseases with astrocyte subtypes and psychotropic medications. https://doi.org/10.1101/2021.09.22.461367

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