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

Mishra, Nibha, Friedson, Lyndon, Hanin, Geula, Bekenstein, Uriya, Volovich, Meshi, Bennett, Estelle R., Greenberg, David S., Soreq, Hermona·2017·Scientific Reports
DOI 10.1038/srep42755PMC PMC5314396
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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.

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Metadata

Authors
Mishra, N., Friedson, L., Hanin, G., Bekenstein, U., Volovich, M., Bennett, E. R., Greenberg, D. S., & Soreq, H.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-02-17
Volume
7
Issue
1
ISSN
2045-2322
DOI
10.1038/srep42755
PMC
PMC5314396
Cited by
29
References
4
Language
en
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