Host microbiota regulates central nervous system serotonin receptor 2C editing in rodents

Loading...
Thumbnail Image
Date
2019-08-15
Authors
van de Wouw, Marcel
Stilling, Roman M.
Peterson, Veronica L.
Ryan, Feargal J.
Hoban, Alan E.
Shanahan, Fergus
Clarke, Gerard
Claesson, Marcus J.
Dinan, Timothy G.
Cryan, John F.
Journal Title
Journal ISSN
Volume Title
Publisher
American Chemical Society
Research Projects
Organizational Units
Journal Issue
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.
Description
Keywords
Germ-free , Microbiota , Serotonin , Serotonin 2C receptor , Editing , Brain
Citation
van de Wouw, M., Stilling, R. M., Peterson, V. L., Ryan, F. J., Hoban, A. E., Shanahan, F., Clarke, G., Claesson, M. J., Dinan, T. G., Cryan, J. F. and Schellekens, H. (2019) 'Host Microbiota Regulates Central Nervous System Serotonin Receptor 2C Editing in Rodents', ACS Chemical Neuroscience, 10(9), pp. 3953-3960. doi: 10.1021/acschemneuro.9b00414
Copyright
© 2019 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Neuroscience, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acschemneuro.9b00414