Non-coding RNAs and Traumatic memories

Professor Hermona Soreq
The Edmond and Lily Safra Center of brain Science and the Life Sciences Institute, The Hebrew University of Jerusalem
Thursday, January 24, 2019 - 12:00pm
Ramsay Wright Building, Room 432
Departmental Seminar
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.
University Professor Marla Sokolowski
Joint EEB/CSB Seminar