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Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair

Miku Aoki1,2, Yoshihisa Watanabe1, Kanji Yoshimoto3

  • 1Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

The European Journal of Neuroscience
|March 8, 2016
PubMed

Insights

Serotonin 2C receptor (5-HT2 C R) RNA editing impacts mood. Non-edited 5-HT2 C R INI mice show depression-like behavior, linked to reduced nucleus accumbens neuropeptide Y (NPY). NPY may regulate mood disorders.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Serotonin 2C receptors (5-HT2 C Rs) are crucial in the central nervous system and linked to neurological disorders.
  • Adenosine-to-inosine RNA editing of 5-HT2 C R mRNA generates 24 isoforms, modulating receptor activity and potentially impacting brain function.
  • Transgenic mice expressing specific 5-HT2 C R isoforms exhibit distinct behavioral and metabolic phenotypes.

Purpose of the Study:

  • To investigate the behavioral and molecular characteristics of transgenic mice expressing the non-edited 5-HT2 C R INI-isoform.
  • To explore the role of RNA editing in modulating serotonergic systems and its relevance to neuropsychiatric disorders.

Main Methods:

  • Behavioral testing, including the forced swimming test, in INI mice.
  • Measurement of serotonin levels in specific brain regions (nucleus accumbens, amygdala, striatum).
  • Analysis of neuropeptide Y (NPY) mRNA expression in the nucleus accumbens.
  • Intervention using adeno-associated virus to overexpress NPY in the nucleus accumbens.

Main Results:

  • INI mice displayed enhanced behavioral despair and increased sensitivity to desipramine.
  • Significantly decreased serotonin levels were observed in the nucleus accumbens, amygdala, and striatum of INI mice.
  • Reduced NPY mRNA expression in the nucleus accumbens was noted.
  • Overexpression of NPY in the nucleus accumbens alleviated behavioral despair.

Conclusions:

  • 5-HT2 C R RNA editing influences serotonergic pathways and behavior.
  • Impaired accumbal NPY expression, potentially regulated by 5-HT2 C R RNA editing, is linked to mood disorders.
  • NPY in the nucleus accumbens may serve as a therapeutic target for mood disorders.
Keywords:
INI-isoform mouseRNA editingaccumbal neuropeptide Ybehavioural despairserotonin 2C receptor

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