title: The stress-inducible actin-interacting protein DRR1 shapes social behavior.
abstract: Understanding the molecular mechanisms by which stress is translated into changes in complex behavior may help to identify novel treatment strategies for stress-associated psychiatric disorders. The tumor suppressor gene down-regulated in renal cell carcinoma 1 (DRR1) was recently characterized as a new molecular link between stress, synaptic efficacy and behavioral performance, most likely through its ability to modulate actin dynamics. The lateral septum is one of the brain regions prominently involved in the stress response. This brain region features high DRR1 expression in adult mice, even under basal conditions. We therefore aimed to characterize and dissect the functional role of septal DRR1 in modulating complex behavior. DRR1 protein expression was shown to be expressed in both neurons and astrocytes of the lateral septum of adult mice. Septal DRR1 mRNA expression increased after acute defeat stress and glucocorticoid receptor activation. To mimic the stress-induced DRR1 increase in the lateral septum of mice, we performed adenovirus-mediated region-specific overexpression of DRR1 and characterized the behavior of these mice. Overexpression of DRR1 in the septal region increased sociability, but did not change cognitive, anxiety-like or anhedonic behavior. The observed changes in social behavior did not involve alterations of the expression of vasopressin or oxytocin receptors, the canonical social neuropeptidergic circuits of the lateral septum. In summary, our data suggest that the stress-induced increase of DRR1 expression in the lateral septum could be a protective mechanism to buffer or counterbalance negative consequences of stress exposure on social behavior.
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany. Electronic address: Merce.Masana@unimedizin-mainz.de.
authors.forename: Mercè
authors.initials: M
authors.lastname: Masana
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany; Institute of Mental Health, Peking University, China; Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China.
authors.forename: Yun-Ai
authors.initials: YA
authors.lastname: Su
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Liebl
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Jansen
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Westerholz
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Klaus V
authors.initials: KV
authors.lastname: Wagner
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Christiana
authors.initials: C
authors.lastname: Labermaier
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Sebastian H
authors.initials: SH
authors.lastname: Scharf
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Santarelli
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Hartmann
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Theo
authors.initials: T
authors.lastname: Rein
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Müller
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D012919:Social Behavior; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D000199:Actins; C549076:DRR1 protein, mouse; D025521:Tumor Suppressor Proteins; D003907:Dexamethasone
keywords: Actin; DRR1; Fam107A; Glucocorticoids; Lateral septum; Mice; Resilience; Social behavior; Stress; Tu3A