Gene Enrichment Analysis of Astrocyte Subtypes in Psychiatric Disorders and Psychotropic Medication Datasets

作者：Xiaolu Zhang, Alyssa Wolfinger, Xiaojun Wu, Rawan Alnafisah, Ali Sajid Imami, Abdul‐rizaq Hamoud, Anna Lundh, Vladimir Parpura, Robert E. McCullumsmith, Rammohan Shukla, Sinead M. O’Donovan · 发表于：Cells · 年份：2022 · DOI：10.3390/cells11203315 · 被引用次数：8 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Tryptophan and brain disorders、Immune cells in cancer

Astrocytes have many important functions in the brain, but their roles in psychiatric disorders and their responses to psychotropic medications are still being elucidated. Here, we used gene enrichment analysis to assess the relationships between different astrocyte subtypes, psychiatric diseases, and psychotropic medications (antipsychotics, antidepressants and mood stabilizers). We also carried out qPCR analyses and "look-up" studies to assess the chronic effects of these drugs on astrocyte marker gene expression. Our bioinformatic analysis identified gene enrichment of different astrocyte subtypes in psychiatric disorders. The highest level of enrichment was found in schizophrenia, supporting a role for astrocytes in this disorder. We also found differential enrichment of astrocyte subtypes associated with specific biological processes, highlighting the complex responses of astrocytes under pathological conditions. Enrichment of protein phosphorylation in astrocytes and disease was confirmed by biochemical analysis. Analysis of LINCS chemical perturbagen gene signatures also found that kinase inhibitors were highly discordant with astrocyte-SCZ associated gene signatures. However, we found that common gene enrichment of different psychotropic medications and astrocyte subtypes was limited. These results were confirmed by "look-up" studies and qPCR analysis, which also reported little effect of psychotropic medications on common astrocyte marker gene expression, suggesting ...