Host Microbiota Regulates Central Nervous System Serotonin Receptor 2C Editing in Rodents

Marcel Van De Wouw, Roman M. Stilling, Veronica L. Peterson, Feargal J. Ryan, Alan E. Hoban, Fergus Shanahan, Gerard Clarke, Marcus J. Claesson, Timothy G. Dinan, John F. Cryan, Harriët Schellekens

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Microbial colonization of the gastrointestinal tract plays a crucial role in the development of enteric and central nervous system functionality. The serotonergic system has been heavily implicated in microbiota-gut-brain axis signaling, particularly in proof-of-principle studies in germ-free (GF) animals. One aspect of the serotonergic system that has been left unexplored in relation to the microbiota is the unique ability of the serotonin receptor 2C (5-HT2C) to undergo post-transcriptional editing, which has been implicated in decreased receptor functionality. We investigated whether GF mice, with absent microbiota from birth, have altered 5-HT2C receptor expression and editing in the brain, and if colonization of the microbiota is able to restore editing patterns. Next, we investigated whether microbiota depletion later in life using a chronic antibiotic treatment could affect 5-HT2C receptor editing patterns in rats. We found that GF mice have an increased prevalence of the edited 5-HT2C receptor isoforms in the amygdala, hypothalamus, prefrontal cortex, and striatum, which was partially normalized upon colonization post-weaning. However, no alterations were observed in the hypothalamus after microbiota depletion using an antibiotic treatment in adult rats. This suggests that alterations in the microbiome during development, but not later in life, could influence 5-HT2C receptor editing patterns. Overall, these results demonstrate that the microbiota affects 5-HT2C receptor editing in the brain and may inform novel therapeutic strategies in conditions in which 5-HT2C receptor editing is altered, such as depression.

Original languageEnglish
Pages (from-to)3953-3960
Number of pages8
JournalACS Chemical Neuroscience
Volume10
Issue number9
DOIs
Publication statusPublished - 18 Sep 2019
Externally publishedYes

Keywords

  • brain
  • editing
  • Germ-free
  • microbiota
  • serotonin
  • serotonin 2C receptor

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