: Hermona Soreq - The Edmond and Lily Safra Center of brain Science and the Life Sciences Institute, The Hebrew University of Jerusalem
Host: Marla Sokolowski
MicroRNAs (miRs), including ‘CholinomiR’ regulators of acetylcholine-mediated messages co-regulate global gene expression to ensure homeostasis via cooperative context-dependent activities. In experimental mice, the stress-inducible master regulator miR-132 limits trauma-induced cognitive impairments by targeting the acetylcholine hydrolyzing enzyme acetylcholinesterase (AChE). However, transgenic mice with excess miR-132 accumulate hepatic lipids, and antisense suppression of miR-132 retracts hepatic hyperlipidemia in diet-fattened mice. In humans, single nucleotide polymorphisms (SNPs) interrupting CholinomiR functioning modify traumatic responses: disrupted interaction of the primate-specific miR-608/AChE associates with elevated anxiety, blood pressure and inflammation, but also protective over-activation of prefrontal lobe reaction to stressors. Moreover, aging ex-war prisoner carriers of SNPs interrupting miR-608/AChE interaction presented limited symptoms and serum exosome miRs reflecting them. Furthermore, brains of Bipolar Disorder (BD) and Schizophrenia (SCZ) patients showed sex-dependent cholinergic transcript differences, validated in human-originated neuronal cells under cholinergic differentiation. CholinomiRs-mediated suppression of stress-inducible impairments may hence modulate reactions to multiple traumatic, metabolic and mental conditions, opening new venues for finding novel disease biomarkers and therapeutic targets.