The Hebrew University of Jerusalem
MicroRNAs (miRs) orchestrate brain and body functioning via interaction with and suppression of target transcripts. We study how miR controllers of cholinergic signaling (‘CholinomiRs’) affect health and disease (1) by combining mouse engineering, Surface Plasmon Resonance, RNA-sequencing and experimental interference tests. We discovered that anxiety-related CholinomiRs suppress inflammation (2) but potentiate metabolic processes (3). In humans, anxiety, inflammation and metabolic disorders are inter-related (4). Correspondingly, a single nucleotide polymorphism (SNP) interrupting acetylcholinesterase control by the primate-specific CholinomiR-608 associates with elevated anxiety, inflammation and blood pressure (5) and with exacerbated pre-frontal cortical fMRI response to stressful insults (6). Furthermore, neurodegenerative disease patients carrying CholinomiR-interrupting SNPs may suffer excessive neuroinflammation (7). Reciprocally, elevating CholinomiR-132 in mouse peripheral tissues modulates the balance between acetylcholinesterase splice variants (8) and induces liver hyperlipidemia that was antisense oligonucleotide-suppressible (9). Our findings identify an intriguing tradeoff between anxiety and metabolic CholinomiR effects, implicating body-brain messages in balancing mental and metabolic processes and calling for personalized medicine of the accompanying disorders.
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