Prof. Hermona Soreq

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

Mishra, N, Friedson L, Hanin G, Bekenstein U, Volovich M, Bennett ER, Greenberg DS, Soreq H.  2017.  

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.

Journal:

Sci Rep

Volume:

7

Pagination:

42755

Date Published:

Feb 17

Notes:

2045-2322Mishra, NibhaFriedson, LyndonHanin, GeulaBekenstein, UriyaVolovich, MeshiBennett, Estelle RGreenberg, David SSoreq, HermonaERC_321501/European Research Council/InternationalJournal ArticleEnglandSci Rep. 2017 Feb 17;7:42755. doi: 10.1038/srep42755.