Potential Impact of Hypoxic Astrocytes on the Aggravation of Depressive Symptoms in Parkinson ’s Disease

In this study, we presented our findings demonstrating distinct characteristics of cortical astrocy tes in PD patients compared to reactivated glial cells in the substantia nigra. We identified a subset of differentially expressed genes associated with depressive disorders from PD-associated cortical astrocytes. Furthermore, we uncovered the potential involvement of the hypoxia signaling in drivin g cortical astrocytic dysfunctions. Through a comprehensive investigation utilizing transcriptome and chromatin accessibility analyses on cultured human astrocytes, we revealed that hypoxic treatment could induce similar expression changes observed in cortex from PD patients. Additionally, we provid ed evidence that activation of the HIF-1 signaling pathway suppressed the expression of key components of mitochondrial ribosomes and electron transport chain proteins COX2 and CYTB, resulting in abnormal mitochondrial membrane potential. Our results underscore the potential impact of glial metaboli c abnormalities on the development of depressive disorders associated with Parkinson’s disease.
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research