Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair. (5th April 2016)

• Record Type: Journal Article
• Authors: Aoki, Miku; Watanabe, Yoshihisa; Yoshimoto, Kanji; Tsujimura, Atsushi; Yamamoto, Toshiro; Kanamura, Narisato; Tanaka, Masaki
• Editors: Isles, Anthony
• Is Part Of: European journal of neuroscience. Volume 43:Number 9(2016:May)
• Page Start: 1219
• Page End: 1228
• Publication Date: 2016-04-05
• Subjects: accumbal neuropeptide Y -- behavioural despair -- INI‐isoform mouse -- RNA editing -- serotonin 2C receptor; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13233
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Serotonin 2C receptors (5‐HT2 C Rs) are widely expressed in the central nervous system, and are associated with various neurological disorders. 5‐HT2 C R mRNA undergoes adenosine‐to‐inosine RNA editing at five sites within its coding sequence, resulting in expression of 24 different isoforms. Several edited isoforms show reduced activity, suggesting that RNA editing modulates serotonergic systems in the brain with causative relevance to neuropsychiatric disorders. Transgenic mice solely expressing the non‐edited 5‐HT2 C R INI‐isoform (INI) or the fully edited VGV‐isoform exhibit various phenotypes including metabolic abnormalities, aggressive behaviour, anxiety‐like behaviour, and depression‐like behaviour. Here, we examined the behavioural phenotype and molecular changes of INI mice on a C57BL/6J background. INI mice showed an enhanced behavioural despair in the forced swimming test, elevated sensitivity to the tricyclic antidepressant desipramine, and significantly decreased serotonin in the nucleus accumbens (NAc), amygdala, and striatum. They also showed reduced expression of neuropeptide Y (NPY) mRNA in the NAc. In addition, by stereotactic injection of adeno‐associated virus encoding NPY into the NAc, we demonstrated that accumbal NPY overexpression relieved behavioural despair. Our results suggest that accumbal NPY expression may be regulated by 5‐HT2 C R RNA editing, and its impairment may be linked to mood disorders. Abstract : Transgenic mice solely expressing the non‐edited 5‐HT2 C R INI‐isoform showed an enhanced behavioral despair and elevated sensitivity to desipramine in forced swim test (FST), and significantly decreased 5‐HT in the nucleus accumbens (NAc), amygdala, and striatum. Furthermore, they also showed reduced expression of neuropeptide Y (NPY) mRNA in the NAc. By stereotactic injection of adeno‐associated virus (AAV) encoding NPY into the NAc, we demonstrate that accumbal NPY overexpression relieves behavioral despair.