Chronic oxytocin-driven alternative splicing of Crfr2α induces anxiety

• DOI: 10.1038/s41380-021-01141-x
• Publication Date: 2021-05-25T12:03:30Z
• Authors: Julia Winter; Magdalena Meyer; Ilona Berger; Melanie Royer; Marta Bianchi; Kerstin Kuffner; Sebastian Peters; Simone Stang; Dominik Langgartner; Finn Hartmann; Anna K. Schmidtner; Stefan O. Reber; Oliver J. Bosch; Anna Bludau; David A. Slattery; Erwin H. van den ...; Benjamin Jurek; Inga D. Neumann
• Keywords: Anxiogenic; Oxytocin receptor

Abstract The neuropeptide oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including anxiety and autism spectrum disorders. However, the behavioral molecular consequences associated with chronic OXT receptor (OXTR) activation have scarcely been studied, despite therapeutic long-term use of intranasal OXT. Here, we reveal that over two weeks increased anxiety-like behavior in rats, higher sensitivity females, contrasting well-known anxiolytic effect acute increase was transient waned 5 days after infusion ended. effects were paralleled by an intracellular signaling pathway, which ultimately led to alternative splicing hypothalamic corticotropin-releasing factor 2α ( Crfr2α ), important modulator anxiety. In detail, shifted ratio from membrane-bound (mCRFR2α) form CRFR2α towards soluble (sCRFR2α) form. Experimental induction mimicked anxiogenic OXT, while sCRFR2α-knock down reduced anxiety-related male rats. Furthermore, triggered release sCRFR2α into cerebrospinal fluid levels positively correlating behavior. summary, revealed expression underlies adverse on