title: Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism.
abstract: Impaired 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.
authors: Center for Behavioral Neuroscience, Institute of Experimental Psychology, University of Düsseldorf, 40225 Düsseldorf, Germany.
authors: Maria A
authors: MA
authors: de Souza Silva
authors: Bernd
authors: B
authors: Lenz
authors: Andrea
authors: A
authors: Rotter
authors: Teresa
authors: T
authors: Biermann
authors: Oliver
authors: O
authors: Peters
authors: Alfredo
authors: A
authors: Ramirez
authors: Frank
authors: F
authors: Jessen
authors: Wolfgang
authors: W
authors: Maier
authors: Michael
authors: M
authors: Hüll
authors: Johannes
authors: J
authors: Schröder
authors: Lutz
authors: L
authors: Frölich
authors: Stefan
authors: S
authors: Teipel
authors: Oliver
authors: O
authors: Gruber
authors: Johannes
authors: J
authors: Kornhuber
authors: Joseph P
authors: JP
authors: Huston
authors: Christian P
authors: CP
authors: Müller
authors: Sandra
authors: S
authors: Schäble
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology* / Q000523:psychology*; D000818:Animals; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D060825:Cognitive Dysfunction / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D003704:Dementia / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D023421:Models, Animal; D008959:Models, Neurological; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D018042:Receptors, Neurokinin-3; D000109:Acetylcholine
keywords: in vivo microdialysis; senktide
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