Depression-resistant Phenotype in Mice Overexpressing Regulator of G Protein Signaling 8 (RGS8)

Neuroscience
Yuki KobayashiYumiko Saito

Abstract

Regulator of G protein signaling (RGS) proteins are negative regulators of heterotrimeric G proteins that act by accelerating Gα-mediated GTPase activity to terminate G protein-coupled receptor-associated signaling. RGS8 is expressed in several brain regions involved with movement and mood. To investigate the role of RGS8 in vivo, we generated transgenic mice overexpressing brain RGS8 (RGS8tg). RGS8 gene and protein expressions were examined by real-time PCR and immunohistochemistry, respectively, and a significant increase in RGS8 protein was detected in the hippocampal CA1 region compared with wild-type mice (WT). We characterized the phenotypic traits, and found that RGS8tg showed decreased depressive-like behavior in the forced swimming test (FST). Previously, RGS8 was identified as a potent negative regulator of melanin-concentrating hormone receptor 1 (MCHR1), whose activation is mainly involved in energy homeostasis and emotional processing. Interestingly, acute oral administration of MCHR1 antagonist SNAP94847 did not have antidepressant-like effects on RGS8tg in the FST, but did show antidepressant effects on WT. In contrast, selective noradrenaline reuptake inhibitor desipramine had a significant effect on RGS8tg in t...Continue Reading

Citations

Mar 15, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Masaki Saito, Takeya Sato
Oct 11, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Yumiko SaitoYuki Kobayashi
Nov 30, 2018·Frontiers in Pharmacology·Nicolas B SeneseJohn R Traynor

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