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000137038 0247_ $$2doi$$a10.1073/pnas.1306884110
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000137038 0247_ $$2ISSN$$a1091-6490
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000137038 037__ $$aDZNE-2020-03360
000137038 041__ $$aEnglish
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000137038 1001_ $$0P:(DE-HGF)0$$ade Souza Silva, Maria A$$b0$$eCorresponding author
000137038 245__ $$aNeurokinin3 receptor as a target to predict and improve learning and memory in the aged organism.
000137038 260__ $$aWashington, DC$$bNational Acad. of Sciences$$c2013
000137038 264_1 $$2Crossref$$3online$$bProceedings of the National Academy of Sciences$$c2013-08-27
000137038 264_1 $$2Crossref$$3print$$bProceedings of the National Academy of Sciences$$c2013-09-10
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000137038 520__ $$aImpaired learning and memory performance is often found in aging as an early sign of dementia. It is associated with neuronal loss and reduced functioning of cholinergic networks. Here we present evidence that the neurokinin3 receptors (NK3-R) and their influence on acetylcholine (ACh) release may represent a crucial mechanism that underlies age-related deficits in learning and memory. Repeated pharmacological stimulation of NK3-R in aged rats was found to improve learning in the water maze and in object-place recognition. This treatment also enhanced in vivo acetylcholinergic activity in the frontal cortex, hippocampus, and amygdala but reduced NK3-R mRNA expression in the hippocampus. Furthermore, NK3-R agonism incurred a significantly higher increase in ACh levels in aged animals that showed superior learning than in those that were most deficient in learning. Our findings suggest that the induced activation of ACh, rather than basal ACh activity, is associated with superior learning in the aged. To test whether natural variation in NK3-R function also determines learning and memory performance in aged humans, we investigated 209 elderly patients with cognitive impairments. We found that of the 15 analyzed single single-nucleotide ploymorphism (SNPs) of the NK3-R-coding gene, TACR3, the rs2765 SNP predicted the degree of impairment of learning and memory in these patients. This relationship could be partially explained by a reduced right hippocampus volume in a subsample of 111 tested dementia patients. These data indicate the NK3-R as an important target to predict and improve learning and memory performance in the aged organism.
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000137038 650_7 $$2NLM Chemicals$$aRNA, Messenger
000137038 650_7 $$2NLM Chemicals$$aReceptors, Neurokinin-3
000137038 650_7 $$0N9YNS0M02X$$2NLM Chemicals$$aAcetylcholine
000137038 650_2 $$2MeSH$$aAcetylcholine: physiology
000137038 650_2 $$2MeSH$$aAged
000137038 650_2 $$2MeSH$$aAged, 80 and over
000137038 650_2 $$2MeSH$$aAging: genetics
000137038 650_2 $$2MeSH$$aAging: physiology
000137038 650_2 $$2MeSH$$aAging: psychology
000137038 650_2 $$2MeSH$$aAnimals
000137038 650_2 $$2MeSH$$aCognition Disorders: genetics
000137038 650_2 $$2MeSH$$aCognition Disorders: physiopathology
000137038 650_2 $$2MeSH$$aCognition Disorders: psychology
000137038 650_2 $$2MeSH$$aCognitive Dysfunction: genetics
000137038 650_2 $$2MeSH$$aCognitive Dysfunction: physiopathology
000137038 650_2 $$2MeSH$$aCognitive Dysfunction: psychology
000137038 650_2 $$2MeSH$$aDementia: genetics
000137038 650_2 $$2MeSH$$aDementia: physiopathology
000137038 650_2 $$2MeSH$$aDementia: psychology
000137038 650_2 $$2MeSH$$aFemale
000137038 650_2 $$2MeSH$$aGenetic Association Studies
000137038 650_2 $$2MeSH$$aHumans
000137038 650_2 $$2MeSH$$aLearning: drug effects
000137038 650_2 $$2MeSH$$aLearning: physiology
000137038 650_2 $$2MeSH$$aMale
000137038 650_2 $$2MeSH$$aMaze Learning: drug effects
000137038 650_2 $$2MeSH$$aMaze Learning: physiology
000137038 650_2 $$2MeSH$$aMemory: drug effects
000137038 650_2 $$2MeSH$$aMemory: physiology
000137038 650_2 $$2MeSH$$aMiddle Aged
000137038 650_2 $$2MeSH$$aModels, Animal
000137038 650_2 $$2MeSH$$aModels, Neurological
000137038 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide
000137038 650_2 $$2MeSH$$aRNA, Messenger: genetics
000137038 650_2 $$2MeSH$$aRNA, Messenger: metabolism
000137038 650_2 $$2MeSH$$aRats
000137038 650_2 $$2MeSH$$aRats, Wistar
000137038 650_2 $$2MeSH$$aReceptors, Neurokinin-3: agonists
000137038 650_2 $$2MeSH$$aReceptors, Neurokinin-3: genetics
000137038 650_2 $$2MeSH$$aReceptors, Neurokinin-3: physiology
000137038 7001_ $$aLenz, Bernd$$b1
000137038 7001_ $$aRotter, Andrea$$b2
000137038 7001_ $$aBiermann, Teresa$$b3
000137038 7001_ $$0P:(DE-HGF)0$$aPeters, Oliver$$b4
000137038 7001_ $$0P:(DE-HGF)0$$aRamirez, Alfredo$$b5
000137038 7001_ $$0P:(DE-2719)2000032$$aJessen, Frank$$b6$$udzne
000137038 7001_ $$0P:(DE-2719)2000015$$aMaier, Wolfgang$$b7$$udzne
000137038 7001_ $$aHüll, Michael$$b8
000137038 7001_ $$aSchröder, Johannes$$b9
000137038 7001_ $$aFrölich, Lutz$$b10
000137038 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan$$b11$$udzne
000137038 7001_ $$0P:(DE-HGF)0$$aGruber, Oliver$$b12
000137038 7001_ $$aKornhuber, Johannes$$b13
000137038 7001_ $$aHuston, Joseph P$$b14
000137038 7001_ $$aMüller, Christian P$$b15
000137038 7001_ $$aSchäble, Sandra$$b16
000137038 77318 $$2Crossref$$3journal-article$$a10.1073/pnas.1306884110$$b : Proceedings of the National Academy of Sciences, 2013-08-27$$n37$$p15097-15102$$tProceedings of the National Academy of Sciences$$v110$$x0027-8424$$y2013
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