Short communicationsMicrobial regulation of hippocampal miRNA expression: Implications for transcription of kynurenine pathway enzymes
Section snippets
Sex and germ free status interact to alter the expression of miRNA’s
Microarray analysis was performed on hippocampi removed from both male and female conventional (CON), germ free (GF) and mice that had previously been germ free but were colonised (exGF) post-weaning (day 21), (Fig. 1A). Microarray analysis revealed that microbial colonisation status and sex affected the expression of hippocampal miRNAs (Fig. 1B). A two-way analysis of variance (ANOVA) analysis revealed a significant interaction between sex and colonisation status in 15 miRNAs (Table 2).
mir-294-5p expression in the hippocampus is regulated by the gut microbiota
To validate our microarray results, we performed qRT-PCR on hippocampal RNA from the same mice from the microarray experiment. Based on the results of the two-way ANOVA and using specific primers for 3 miRNAs mmu-miR-342-3p, mmu-miR-294-5p and mmu-miR-16-5p (Table 1), we found a significant increase in expression of miR-294-5p only in the hippocampus of male mice compared to conventionally raised male mice (Fig. 2C, p < 0.05). This increase in gene expression was reversed upon colonisation of
mir-294-5p targets the kynurenine pathway enzymes
Considering these results and the role the gut microbiota plays in other regions of the brain, we wanted to understand what genes were targeted by the miRNAs listed in Table 2, and what potential pathways they may be involved in. Specifically, we investigated if those miRNAs that displayed a significant interaction in relation to germ free status and sex (Table 2) were overrepresented in the tryptophan catabolic process to kynurenine pathway (GO: 0019441), as recent data from our group has
Funding
The APC Microbiome Institute is a research centre funded by Science Foundation Ireland, through the Irish Government’s National Development Plan Dr Clarke reported that his research is supported by Science Foundation Ireland (SFI) (grant number SFI/12/RC/2273) and by the Health Research Board (HRB) through Health Research Awards (grant number HRA-POR-2-14-647; GC). GC is supported by a NARSAD Young Investigator Grant from the Brain and Behaviour Research Foundation grant number (20771). Prof
Acknowledgements
We acknowledge the contribution of Ms Frances O’Brien and Patrick Fitzgerald in this study. This manuscript results in part from collaboration and network activities promoted under the frame of the international network GENIEUR (Genes in Irritable Bowel Syndrome Research Network Europe), which has been funded by the COST program (BM1106, www.GENIEUR.eu) and is currently supported by the European Society of Neurogastroenterology and Motility (ESNM, www.ESNM.eu). Eloisa Salvo-Romero received a
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