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@ARTICLE{deSouzaSilva:137038,
author = {de Souza Silva, Maria A and Lenz, Bernd and Rotter, Andrea
and Biermann, Teresa and Peters, Oliver and Ramirez, Alfredo
and Jessen, Frank and Maier, Wolfgang and Hüll, Michael and
Schröder, Johannes and Frölich, Lutz and Teipel, Stefan
and Gruber, Oliver and Kornhuber, Johannes and Huston,
Joseph P and Müller, Christian P and Schäble, Sandra},
title = {{N}eurokinin3 receptor as a target to predict and improve
learning and memory in the aged organism.},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {110},
number = {37},
issn = {0027-8424},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {DZNE-2020-03360},
pages = {15097-15102},
year = {2013},
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.},
keywords = {Acetylcholine: physiology / Aged / Aged, 80 and over /
Aging: genetics / Aging: physiology / Aging: psychology /
Animals / Cognition Disorders: genetics / Cognition
Disorders: physiopathology / Cognition Disorders: psychology
/ Cognitive Dysfunction: genetics / Cognitive Dysfunction:
physiopathology / Cognitive Dysfunction: psychology /
Dementia: genetics / Dementia: physiopathology / Dementia:
psychology / Female / Genetic Association Studies / Humans /
Learning: drug effects / Learning: physiology / Male / Maze
Learning: drug effects / Maze Learning: physiology / Memory:
drug effects / Memory: physiology / Middle Aged / Models,
Animal / Models, Neurological / Polymorphism, Single
Nucleotide / RNA, Messenger: genetics / RNA, Messenger:
metabolism / Rats / Rats, Wistar / Receptors, Neurokinin-3:
agonists / Receptors, Neurokinin-3: genetics / Receptors,
Neurokinin-3: physiology / RNA, Messenger (NLM Chemicals) /
Receptors, Neurokinin-3 (NLM Chemicals) / Acetylcholine (NLM
Chemicals)},
cin = {AG Jessen / U Clinical Researchers - Bonn / Clinical
Dementia Research Rostock /Greifswald ; AG Teipel},
ddc = {500},
cid = {I:(DE-2719)1011102 / I:(DE-2719)7000001 /
I:(DE-2719)1510100},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23983264},
pmc = {pmc:PMC3773732},
doi = {10.1073/pnas.1306884110},
url = {https://pub.dzne.de/record/137038},
}