Glucocorticoid signalling affects astrocyte function via long non-coding RNAs

Glucocorticoid signalling serves as a central regulator of the body's stress response and has been associated with several diseases affecting the central nervous system (CNS), such as major depressive disorder or Alzheimer’s disease. While the cell type-specific effect of glucocorticoids in the CNS has been studied previously, our understanding of how glucocorticoids act on astrocytes and their impact on neuronal network plasticity is limited. It's important to note that only 1.5% of the genome encodes proteins, while the remaining 98.5% consists of non-coding RNAs (ncRNAs) implicated in various cellular functions. In this study we aimed to identify glucocorticoid-induced lncRNAs in astrocytes. Differential Gene Expression Analysis revealed a number of deregulated genes and lncRNAs, with several of them validated through RT-qPCR. For functional analysis we generated GapmeRs to knock down candidate lncRNAs with minimal off target effects and performed several assays to study astrocyte phenotypes and neuronal network activity. Our data suggest that the regulation of lncRNAs plays an important role in orchestrating the astroglia response to glucocorticoid signaling.