Estrela, Karolyne A. R. and Senninger, Lisa and Arndt, Josephine and Kabas, Melanie and Schmid, Ferdinand and Dillmann, Larissa and Auer, Sophia and Stepfer, Thomas and Flor, Peter J. and Uschold-Schmidt, Nicole (2022) Blocking Metabotropic Glutamate Receptor Subtype 7 via the Venus Flytrap Domain Promotes a Chronic Stress-Resilient Phenotype in Mice. CELLS, 11 (11): 1817. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)Abstract
Chronic psychosocial stress participates prominently in the etiology of various psychiatric conditions and comorbid somatic pathologies; however, suitable pharmacotherapy of these disorders is still of high medical need. During the last few decades, research on mGlu receptors advanced remarkably and much attention was given to the mGlu7 subtype. Here, genetic mGlu7 ablation, short-term pharmacological mGlu7 blockade, as well as siRNA-mediated knockdown of mGlu7 were shown to result in an acute anti-stress, antidepressant- and anxiolytic-like phenotype in mice. Moreover, we recently revealed a prominent stress-protective effect of genetic mGlu7 ablation also with respect to chronic psychosocial stress. In addition, we are able to demonstrate in the present study that the chronic pharmacological blockade of mGlu7 interferes with various chronic stress-induced alterations. For this, we used the chronic subordinate colony housing (CSC), a mouse model of chronic male subordination, in combination with chronic treatment with the mGlu7-selective orthosteric-like antagonist XAP044 (7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one). Interestingly, XAP044 dose-dependently ameliorates hypothalamic-pituitary-adrenal axis dysfunctions, thymus atrophy, as well as the CSC-induced increase in innate anxiety. Taken together, our findings provide further evidence for the role of mGlu7 in chronic psychosocial stress-induced alterations and suggests the pharmacological blockade of mGlu7 as a promising therapeutic approach for the treatment of chronic stress-related pathologies in men.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC PSYCHOSOCIAL STRESS; MESSENGER-RNA; ADULT-RAT; IN-VITRO; HPA AXIS; ANXIETY; BRAIN; CONSEQUENCES; LOCALIZATION; EXTINCTION; mGlu7; XAP044; chronic psychosocial stress; chronic subordinate colony housing |
| Subjects: | 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie > Molecular and Cellular Neurobiology (Prof. Dr. Peter J. Flor) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Dec 2023 16:06 |
| Last Modified: | 12 Dec 2023 16:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57034 |
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