Muscarinic-dependent miR-182 and QR2 expression regulation in the anterior insula enables novel taste learning

מאת: Gould N.L., Elkobi A., Edry E., Daume J., Rosenblum K.
פורסם ב: eNeuro
תיאור: In a similar manner to other learning paradigms, intact muscarinic acetylcholine receptor (mAChR) neurotrans-mission orprotein synthesis regulation in the anterior insular cortex (aIC) is necessary for appetitive taste learning. Here we describe a parallel local molecular pathway, where GABAA receptor control of mAChR activation causes upregulation of miRNA-182 and quinone reductase 2 (QR2) mRNA destabilization in the rodent aIC. Damage to long-term memory by prevention of this process, with the use of mAChR antagonist scopola-mine before novel taste learning, can be rescued by local QR2 inhibition, demonstrating that QR2 acts down-stream of local muscarinic activation. Furthermore, we prove for the first time the presence of endogenous QR2 cofactors in the brain, establishing QR2 as a functional reductase there. In turn, we show that QR2 activity causes the generation of reactive oxygen species, leading to modulation in Kv2.1 redox state. QR2 expression reduction therefore is a previously unaccounted mode of mAChR-mediated inflammation reduction, and thus adds QR2 to the cadre of redox modulators in the brain. The concomitant reduction in QR2 activity during memory consolidation suggests a complementary mechanism to the well established molecular processes of this phase, by which the cortex gleans important information from general sensory stimuli. This places QR2 as a promising new target to tackle neurodegenerative inflammation and the associated impediment of novel memory formation in diseases such as Alzheimer’s disease. © 2020, Society for Neuroscience. All rights reserved.
SDGs : SDG 03  |  יחידות: מדעי הטבע  | מועד: 2020 |  קישור