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Yang, H.* ; Narayan, S.* ; Bordes, J.* ; van Doeselaar, L.* ; De Donno, C. ; Eder, M.* ; Menegaz, D.* ; Huettl, R.E.* ; Brix, L.M.* ; Mitra, S.* ; Springer, M.* ; Müller, M.B.* ; Chen, A.* ; Deussing, J.M.* ; Lopez, J.P.* ; Schmidt, M.V.*

Mineralocorticoid receptor in glutamatergic neurons modulates anxiety exclusively in male mice via regulation of the actin-bundling factor Fam107a.

Biol. Psychiatry Glob. Open. Sci. 6:100651 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Background Exposure to stressful life events is a major risk factor for many psychiatric disorders. The mineralocorticoid receptor (MR) is a key regulator of the hypothalamic-pituitary-adrenal axis, a central stress response component. Stress-related mental disorders, such as anxiety and depression, are associated with MR dysfunction in the brain, but its cell type–specific contributions to emotional behavior and cognitive function remain unclear. Methods Using a mouse model with a specific deletion of MR in forebrain glutamatergic neurons, we tested the behavioral, structural, and functional impact of MR in this neuronal population ( n = 9–14 for behavioral and n = 3–4 for structural and functional analyses). Results We revealed a specific function of MR in regulating baseline anxiety in male but not female mice. This distinct behavioral phenotype was associated with hippocampal structural and functional alterations. Furthermore, we identified a previously unrecognized downstream target of MR, the actin-bundling factor Fam107a, whose expression is tightly regulated by MR. Overexpression of Fam107a in the hippocampus was sufficient to rescue the increased anxiety phenotype of glutamatergic MR knockout mice. Conclusions Together, our results underline the central role of MR as a potential target in understanding the intricate interplay between stress, resilience, and mental health.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Anxiety ; Behavior ; Memory ; Mineralocorticoid Receptor ; Sex ; Stress; Social Defeat Stress; Sex-differences; Nervous-system; Behavior; Brain; Overexpression; Corticosterone; Neuroendocrine; Hippocampus; Cancer
ISSN (print) / ISBN 2667-1743
e-ISSN 2667-1743
Journal Biological Psychiatry Global Open Science
Quellenangaben Volume: 6, Issue: 2, Pages: , Article Number: 100651 Supplement: ,
Publisher Elsevier
Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants China Scholarship Council