Analysis of the hypothalamic oxytocin system and oxytocin receptor‐expressing astrocytes in a mouse model of Prader–Willi syndrome. (1st December 2022)

• Record Type: Journal Article
• Authors: Althammer, Ferdinand; Wimmer, Moritz Claudius; Krabichler, Quirin; Küppers, Stephanie; Schimmer, Jonas; Fröhlich, Henning; Dötsch, Laura; Gruber, Tim; Wunsch, Selina; Schubert, Tim; Kirchner, Matthew K.; Stern, Javier E.; Charlet, Alexandre; Grinevich, Valery; Schaaf, Christian P.
• Is Part Of: Journal of neuroendocrinology. Volume 34:Number 12(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-01
• Subjects: astrocytes -- oxytocin -- Prader‐Willi syndrome -- Schaaf‐Yang syndrome; Neuroendocrinology -- Periodicals; 616.4
• DOI: 10.1111/jne.13217
• Languages: English
• ISSNs: 0953-8194

Abstract

Abstract: Prader–Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hyperphagia, obesity, developmental delay and intellectual disability. Studies suggest dysfunctional signaling of the neuropeptide oxytocin as one of the key mechanisms in PWS, and administration of oxytocin via intranasal or systemic routes yielded promising results in both humans and mouse models. However, a detailed assessment of the oxytocin system in mouse models of PWS such as the Magel2‐deficient Magel2 tm1.Stw mouse, is lacking. In the present study, we performed an automated counting of oxytocin cells in the entire paraventricular nucleus of the hypothalamus of Magel2 tm1.Stw and wild‐type control mice and found a significant reduction in the caudal part, which represents the parvocellular subdivision. In addition, based on the recent discovery that some astrocytes express the oxytocin receptor (OTR), we performed detailed analysis of astrocyte numbers and morphology in various brain regions, and assessed expression levels of the astrocyte marker glial fibrillary acidic protein, which was significantly decreased in the hypothalamus, but not other brain regions in Magel2 tm1.Stw mice. Finally, we analyzed the number of OTR‐expressing astrocytes in various brain regions and found a significant reduction in the nucleus accumbens of Magel2 tm1.Stw mice, as well as a sex‐specific difference in the lateral septum. This study suggests a role for caudal paraventricular nucleus oxytocin neurons as well as OTR‐expressing astrocytes in a mouse model of PWS, provides novel information about sex‐specific expression of astrocytic OTRs, and presents several new brain regions containing OTR‐expressing astrocytes in the mouse brain. Abstract : If and how genetic disorders such as Prader‐Willi (PWS) or Schaaf‐Yang (SYS) syndromes affect oxytocinergic signaling is not well studied. In this study we used our established and well‐characterised Magel2 KO mouse model and analysed the number of oxytocin (OT) cells and OT receptor‐expressing (OTR) astrocytes. We found a significant reduction in the number of OT cells located in the PVN in Magel2 KO mouse, as well as a reduction of OTR‐positive astrocytes in the nucleus accumbens. Thus, our results provide first evidence that astrocytic OTR signaling might be altered in PWS and SYS.