Expression of quinone reductase-2 in the cortex is a muscarinic acetylcholine receptor-dependent memory consolidation constraint

Akiva N. Rappaport, Eyal Jacob, Vijendra Sharma, Sharon Inberg, Alina Elkobi, Hadile Ounallah-Saad, Metsada Pasmanik-Chor, Efrat Edry, Kobi Rosenblum

Research output: Contribution to journalArticlepeer-review

Abstract

Learning of novel information, including novel taste, requires activation of neuromodulatory transmission mediated, for example, by the muscarinic acetylcholine receptors (mAChRs) in relevant brain structures. In addition, drugs enhancing the function of mAChRs are used to treat memory impairment and decline. However, the mechanisms underlying these effects are poorly understood. Here, using quantitative RT-PCR in Wistar Hola rats, we found quinone reductase 2 (QR2) to be expressed in the cortex in an mAChR-dependent manner. QR2 mRNA expression in the insular cortex is inversely correlated with mAChR activation both endogenously, after novel taste learning, and exogenously, after pharmacological manipulation of the muscarinic transmission. Moreover, reducing QR2 expression levels through lentiviral shRNA vectors or activity via inhibitors is sufficient to enhance long-term memories. We also show here that, in patients with Alzheimer’s disease, QR2 is overexpressed in the cortex. It is suggested that QR2 expression in the cortex is a removable limiting factor of memory formation and thus serves as a new target to enhance cognitive function and delay the onset of neurodegenerative diseases.

Original languageEnglish
Pages (from-to)15568-15581
Number of pages14
JournalJournal of Neuroscience
Volume35
Issue number47
DOIs
StatePublished - 25 Nov 2015

Bibliographical note

Publisher Copyright:
© 2015 the authors.

Keywords

  • Cognitive function
  • Cortex
  • Learning
  • Memory consolidation
  • QR2 (NQO2)
  • mAChR

ASJC Scopus subject areas

  • Neuroscience (all)

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