Antisense miR-132 blockade via the AChE-R splice variant mitigates cortical inflammation

Nibha Mishra, Lyndon Friedson, Geula Hanin, Uriya Bekenstein, Meshi Volovich, Estelle R. Bennett, David S. Greenberg, Hermona Soreq*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

MicroRNA (miR)-132 brain-to-body messages suppress inflammation by targeting acetylcholinesterase (AChE), but the target specificity of 3'-AChE splice variants and the signaling pathways involved remain unknown. Using surface plasmon resonance (SPR), we identified preferential miR-132 targeting of soluble AChE-R over synaptic-bound AChE-S, potentiating miR-132-mediated brain and body cholinergic suppression of pro-inflammatory cytokines. Inversely, bacterial lipopolysaccharide (LPS) reduced multiple miR-132 targets, suppressed AChE-S more than AChE-R and elevated inflammatory hallmarks. Furthermore, blockade of peripheral miR-132 by chemically protected AM132 antisense oligonucleotide elevated muscle AChE-R 10-fold over AChE-S, and cortical miRNA-sequencing demonstrated inverse brain changes by AM132 and LPS in immune-related miRs and neurotransmission and cholinergic signaling pathways. In neuromuscular junctions, AM132 co-elevated the nicotinic acetylcholine receptor and AChE, re-balancing neurotransmission and reaching mild muscle incoordination. Our findings demonstrate preferential miR-132-induced modulation of AChE-R which ignites bidirectional brain and body anti-inflammatory regulation, underscoring splice-variant miR-132 specificity as a new complexity level in inflammatory surveillance.

Original languageEnglish
Article number42755
JournalScientific Reports
Volume7
DOIs
StatePublished - 17 Feb 2017

Bibliographical note

Publisher Copyright:
© 2017 The Author(s).

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