Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-31
pubmed:abstractText
An accumulation of amyloid beta peptide (Abeta) due to an imbalance between anabolism and catabolism triggers Alzheimer's disease (AD). Neprilysin is a rate-limiting peptidase, which participates in the catabolism of Abeta in brain. We investigated whether rats continuously infused with thiorphan, a specific inhibitor for neprilysin, into the cerebral ventricle cause cognitive dysfunction, with an accumulation of Abeta in the brain. Thiorphan-infused rats displayed significant cognitive dysfunction in the ability to discriminate in the object recognition test and spatial memory in the water maze test, but not in other hippocampus-dependent learning and memory tasks. Thiorphan infusion also elevated the Abeta40 level in the insoluble fraction of the cerebral cortex, but not that of the hippocampus. There was no significant difference in the nicotine-stimulated release of acetylcholine in the hippocampus between vehicle- and thiorphan-infused rats. These results indicate that continuous infusion of thiorphan into the cerebral ventricle causes cognitive dysfunction by raising the level of Abeta in the cerebral cortex, and suggest that a reduction of neprilysin activity contribute to the deposition of Abeta and development of AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0166-4328
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
83-91
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16360221-Acetylcholine, pubmed-meshheading:16360221-Amyloid beta-Peptides, pubmed-meshheading:16360221-Animals, pubmed-meshheading:16360221-Brain Chemistry, pubmed-meshheading:16360221-Cerebral Cortex, pubmed-meshheading:16360221-Cues, pubmed-meshheading:16360221-Fear, pubmed-meshheading:16360221-Hippocampus, pubmed-meshheading:16360221-Injections, Intraventricular, pubmed-meshheading:16360221-Learning, pubmed-meshheading:16360221-Male, pubmed-meshheading:16360221-Maze Learning, pubmed-meshheading:16360221-Memory, pubmed-meshheading:16360221-Memory, Short-Term, pubmed-meshheading:16360221-Neprilysin, pubmed-meshheading:16360221-Nicotine, pubmed-meshheading:16360221-Nicotinic Agonists, pubmed-meshheading:16360221-Protease Inhibitors, pubmed-meshheading:16360221-Rats, pubmed-meshheading:16360221-Rats, Wistar, pubmed-meshheading:16360221-Recognition (Psychology), pubmed-meshheading:16360221-Thiorphan
pubmed:year
2006
pubmed:articleTitle
Inhibition of neprilysin by thiorphan (i.c.v.) causes an accumulation of amyloid beta and impairment of learning and memory.
pubmed:affiliation
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8560, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't