Linked Life Data

15120860

Source:http://linkedlifedata.com/resource/pubmed/id/15120860

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-5-3
pubmed:abstractText
Alzheimer's disease is characterized by amyloid peptide formation and deposition, neurofibrillary tangles, central cholinergic dysfunction, and dementia; however, the relationship between these parameters is not well understood. We studied the effect of amyloid peptide formation and deposition on central cholinergic function in knock-in mice carrying the human amyloid precursor protein (APP) gene with the Swedish/London double mutation (APP-SL mice) which were crossbred with transgenic mice overexpressing normal (PS1wt) or mutated (M146L; PS1mut) human presenilin-1. APP-SLxPS1mut mice had increased levels of Abeta peptides at 10 months of age and amyloid plaques at 14 months of age while APP-SLxPS1wt mice did not have increased peptide levels and did not develop amyloid plaques. We used microdialysis in 15-27 months old mice to compare hippocampal acetylcholine (ACh) levels in the two mouse lines and found that extracellular ACh levels were slightly but significantly reduced in the APP-SLxPS1mut mice (-26%; P=0.044). Exploratory activity in the open field increased hippocampal ACh release by two-fold in both mouse lines; total and relative increases were not significantly different for the two strains under study. Similarly, infusion of scopolamine (1 microM) increased hippocampal ACh release to a similar extent (3-5-fold) in both groups. High-affinity choline uptake, a measure of the ACh turnover rate, was identical in both mouse lines. Neurons expressing choline acetyltransferase were increased in the septum of APP-SLxPS1mut mice (+26%; P=0.046). We conclude that amyloid peptide production causes a small decrease of extracellular ACh levels. The deposition of amyloid plaques, however, does not impair stimulated ACh release and proceeds without major changes of central cholinergic function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
125
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1009-17
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15120860-Acetylcholine, pubmed-meshheading:15120860-Alzheimer Disease, pubmed-meshheading:15120860-Amyloid beta-Peptides, pubmed-meshheading:15120860-Amyloid beta-Protein Precursor, pubmed-meshheading:15120860-Animals, pubmed-meshheading:15120860-Behavior, Animal, pubmed-meshheading:15120860-Brain, pubmed-meshheading:15120860-Disease Models, Animal, pubmed-meshheading:15120860-Extracellular Fluid, pubmed-meshheading:15120860-Humans, pubmed-meshheading:15120860-Membrane Proteins, pubmed-meshheading:15120860-Mice, pubmed-meshheading:15120860-Mice, Transgenic, pubmed-meshheading:15120860-Microdialysis, pubmed-meshheading:15120860-Muscarinic Antagonists, pubmed-meshheading:15120860-Mutation, pubmed-meshheading:15120860-Neurons, pubmed-meshheading:15120860-Plaque, Amyloid, pubmed-meshheading:15120860-Presenilin-1, pubmed-meshheading:15120860-Scopolamine Hydrobromide
pubmed:year
2004
pubmed:articleTitle
Central cholinergic functions in human amyloid precursor protein knock-in/presenilin-1 transgenic mice.
pubmed:affiliation
Alzheimer Research Group, Bayer Health Care AG, D-42096 Wuppertal, Germany.
pubmed:publicationType
Journal Article, Comparative Study