Work

Mineralocorticoid Receptor in Glutamatergic Neurons Modulates Anxiety Exclusively in Male Mice Via Regulation of the Actin-Bundling Factor Fam107a

Year: 2025

Type: article

Abstract: 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: = 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.

Source: Biological Psychiatry Global Open Science

DOI: 10.1016/j.bpsgos.2025.100651