Microbial regulation of a lincRNA-miRNA-mRNA network in the mouse hippocampus

Area of Science:

• Neuroscience
• Microbiology
• Genetics

Background:

• The gut microbiota plays a crucial role in brain function.
• Dysregulation of microbiota is implicated in psychiatric disorders.
• Understanding molecular mechanisms of microbiota-brain interactions is essential.

Purpose of the Study:

• To elucidate microbiota-regulated long non-coding RNA (lincRNA)-microRNA (miRNA)-messenger RNA (mRNA) networks in the hippocampus.
• To identify key molecular players involved in microbiota-brain axis in the context of psychiatric disorders.
• To investigate the impact of gut microbiota on gene expression related to CREB and Ras/MAPK signaling pathways.

Main Methods:

• Microarray analysis of hippocampal lincRNAs, mRNAs, and miRNAs in specific pathogen-free, germ-free, and colonized germ-free mice.
• Integrated bioinformatics analysis to construct lincRNA-miRNA-mRNA regulatory networks.
• Identification of differentially expressed genes and regulatory interactions.

Main Results:

• Colonization restored the expression of 139 mRNAs, seven miRNAs, and one lincRNA.
• Restored transcripts were significantly enriched in CREB and Ras/MAPK signaling pathways.
• A regulatory network involving 12 lincRNAs, six miRNAs, and 47 mRNAs was constructed, highlighting lincRNA0926-miR-190a-5p-Celf4 as a potentially pivotal interaction.

Conclusions:

• Gut microbiota significantly impacts hippocampal gene expression networks.
• The lincRNA-miRNA-mRNA regulatory network, particularly the lincRNA0926-miR-190a-5p-Celf4 axis, is crucial for microbiota-brain communication.
• Findings provide insights into the molecular basis of gut microbiota's influence on depressive- and anxiety-like behaviors.