Cover Image: This multi-panel visualization illustrates the molecular mechanisms underlying gene silencing induced by glucocorticoid receptor (GR) overexpression, as detailed in Verma, Roy, and Dwivedi's High Priority Research Communication (HPRC) published in this issue (pp. 38–47). The composition integrates the hypothalamic-pituitary-adrenal (HPA) axis (top left), GR activation at the cellular level (top right), and, at the center of the cover, the fundamental molecular process whereby GR-responsive long noncoding RNAs recruit polycomb repressive complex 2 (PRC2) to deposit repressive H3K27me3 marks on chromatin, thereby silencing genes essential for synaptic function. Genome-wide sequencing data (middle and bottom panels) demonstrate the chromosomal distribution of regulated lncRNAs, their enrichment at closed chromatin domains, and their inverse correlation with expression of genes governing synaptic vesicle dynamics and neurotransmission. Together, these integrated analyses establish a novel epigenetic pathway in which GR overexpression induces transcriptional repression via lncRNA-mediated chromatin remodeling. HPA axis dysregulation, often involving altered glucocorticoid receptor expression or function, has been observed in subgroups of patients with various psychiatric and neurodegenerative conditions. Therefore, this mechanism may offer insight into potential pathophysiological processes in these subpopulations. For detailed methodology and interpretation of individual panels, see the full article. Licinio and Wong on pages (1–3) provide editorial perspective on these findings, exploring their significance for understanding stress-induced psychiatric vulnerability and proposing future research directions

The final cover is licensed under Creative Commons Attribution 4.0 International Public License (CC BY 4.0). The license requires: (1) Attribution — Give appropriate credit (creator name, attribution parties, copyright/license/disclaimer notices, and material link), link to the license, and indicate changes made (including previous modifications) in any reasonable manner that does not suggest licensor endorsement. (2) No additional legal or technological restrictions beyond those in the license. Full details: https://creativecommons.org/licenses/by/4.0/. License provided without warranties.

This issue is now available at https://url.genomicpress.com/2p8njsrw.

Article Contents

Table of Contents

Cover Art

Paul J. Lucassen: How does our brain adapt to a changing and often challenging environment? How can we conceptualize brain plasticity in relation to (early) stress, nutrition, exercise, inflammation, and diseases such as depression and dementia?

Beyond the hallmarks of aging: Rethinking what aging is and how we measure it