title: Expression of Quinone Reductase-2 in the Cortex Is a Muscarinic Acetylcholine Receptor-Dependent Memory Consolidation Constraint.
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.
  
  
  CONCLUSIONS
  We found that: (1) quinone reductase 2 (QR2) expression is a muscarinic-receptor-dependent removable constraint on memory formation in the cortex, (2) reducing QR2 expression or activity in the cortex enhances memory formation, and (3) Alzheimer's disease patients overexpressed QR2. We believe that these results propose a new mechanism by which muscarinic acetylcholine receptors affect cognition and suggest that inhibition of QR2 is a way to enhance cognition in normal and pathological conditions.
authors.affiliation: Sagol Department of Neurobiology and.
authors.forename: Akiva N
authors.initials: AN
authors.lastname: Rappaport
authors.affiliation: Sagol Department of Neurobiology and.
authors.forename: Eyal
authors.initials: E
authors.lastname: Jacob
authors.affiliation: Sagol Department of Neurobiology and.
authors.forename: Vijendra
authors.identifier: http://orcid.org/0000-0002-0945-2623
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Sagol Department of Neurobiology and.
authors.forename: Sharon
authors.initials: S
authors.lastname: Inberg
authors.affiliation: Sagol Department of Neurobiology and.
authors.forename: Alina
authors.initials: A
authors.lastname: Elkobi
authors.affiliation: Sagol Department of Neurobiology and.
authors.forename: Hadile
authors.initials: H
authors.lastname: Ounallah-Saad
authors.affiliation: Bioinformatics Unit, George Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel.
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.affiliation: Sagol Department of Neurobiology and Center for Gene Manipulation in the Brain, University of Haifa, Haifa 3498838, Israel, and.
authors.forename: Efrat
authors.initials: E
authors.lastname: Edry
authors.affiliation: Sagol Department of Neurobiology and Center for Gene Manipulation in the Brain, University of Haifa, Haifa 3498838, Israel, and kobir@psy.haifa.ac.il.
authors.forename: Kobi
authors.initials: K
authors.lastname: Rosenblum
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D011808:Quinone Reductases / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*
chemical_list: D011976:Receptors, Muscarinic; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases
keywords: QR2 (NQO2); cognitive function; cortex; learning; mAChR; memory consolidation