Linked Life Data

19625522

Source:http://linkedlifedata.com/resource/pubmed/id/19625522

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2009-7-23
pubmed:abstractText
Downregulation of brain-derived neurotrophic factor (BDNF) in the cortex occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival, synaptic plasticity, and memory, BDNF reduction may contribute to synaptic and cellular loss and memory deficits characteristic of AD. In vitro evidence suggests that amyloid-beta (A beta) contributes to BDNF downregulation in AD, but the specific A beta aggregation state responsible for this downregulation in vivo is unknown. In the present study, we examined cortical levels of BDNF mRNA in three different transgenic AD mouse models harboring mutations in APP resulting in A beta overproduction, and in a genetic mouse model of Down syndrome. Two of the three A beta transgenic strains (APP(NLh) and TgCRND8) exhibited significantly decreased cortical BDNF mRNA levels compared with wild-type mice, whereas neither the other strain (APP(swe)/PS-1) nor the Down syndrome mouse model (Ts65Dn) was affected. Only APP(NLh) and TgCRND8 mice expressed high A beta(42)/A beta(40) ratios and larger SDS-stable A beta oligomers (approximately 115 kDa). TgCRND8 mice exhibited downregulation of BDNF transcripts III and IV; transcript IV is also downregulated in AD. Furthermore, in all transgenic mouse strains, there was a correlation between levels of large oligomers, A beta(42)/A beta(40), and severity of BDNF decrease. These data show that the amount and species of A beta vary among transgenic mouse models of AD and are negatively correlated with BDNF levels. These findings also suggest that the effect of A beta on decreased BDNF expression is specific to the aggregation state of A beta and is dependent on large oligomers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9321-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19625522-Alzheimer Disease, pubmed-meshheading:19625522-Amyloid beta-Peptides, pubmed-meshheading:19625522-Amyloid beta-Protein Precursor, pubmed-meshheading:19625522-Analysis of Variance, pubmed-meshheading:19625522-Animals, pubmed-meshheading:19625522-Blotting, Western, pubmed-meshheading:19625522-Brain, pubmed-meshheading:19625522-Brain-Derived Neurotrophic Factor, pubmed-meshheading:19625522-Disease Models, Animal, pubmed-meshheading:19625522-Down Syndrome, pubmed-meshheading:19625522-Down-Regulation, pubmed-meshheading:19625522-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:19625522-Humans, pubmed-meshheading:19625522-Mice, pubmed-meshheading:19625522-Mice, Transgenic, pubmed-meshheading:19625522-Polymerase Chain Reaction, pubmed-meshheading:19625522-Presenilin-1, pubmed-meshheading:19625522-Protease Nexins, pubmed-meshheading:19625522-RNA, Messenger, pubmed-meshheading:19625522-Receptors, Cell Surface
pubmed:year
2009
pubmed:articleTitle
Decreased brain-derived neurotrophic factor depends on amyloid aggregation state in transgenic mouse models of Alzheimer's disease.
pubmed:affiliation
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural