Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-7-30
pubmed:abstractText
For the purpose of studying the potential neurobehavioral effects of different human apolipoprotein E (apoE) isoforms produced within the brain, transgenic (TG) mice were generated in which human apoE3 or apoE4 isoforms were under control of an astrocyte-specific, glial fibrillary acidic protein promoter and these TG mice were bred back to apoE knockout (KO) mice. Behavioral phenotypes of apoE3 and apoE4 TG mice were derived by conducting a longitudinal study in which apoE3 and apoE4 TG mice were compared with apoE KO and wild-type (WT) mice (all male) on several behavioral measures. Analysis of locomotor activity, "open-field" behaviors, acoustic startle/prepulse inhibition, and elevated plus maze data suggested that the apoE TG/KO groups were more "emotionally reactive" than WT mice, with apoE4 mice typically being the most reactive. The absence of performance differences among groups on the rotating holeboard and water navigation tasks suggested intact reference memory processing in apoE TG/KO mice. However, apoE4 mice were profoundly impaired on a working memory-based protocol in the radial arm maze (11-14 months). Nonassociative factors (sensorimotor capacities or emotionality differences) did not appear to confound interpretation of the learning/memory results. Western blot analysis revealed no alterations in the level of synaptic, neuronal, or glial markers in neocortex or hippocampus and histologic analysis revealed no evidence of Abeta deposition or neuritic plaques in the apoE KO/TG mice. Our findings suggest that apoE4 expression in the brain may have selective deleterious effects on memory function in the absence of typical Alzheimer's-like neuropathology.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-4886
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
326-44
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11476599-Acoustic Stimulation, pubmed-meshheading:11476599-Aging, pubmed-meshheading:11476599-Alzheimer Disease, pubmed-meshheading:11476599-Analysis of Variance, pubmed-meshheading:11476599-Animals, pubmed-meshheading:11476599-Apolipoprotein E3, pubmed-meshheading:11476599-Apolipoprotein E4, pubmed-meshheading:11476599-Apolipoproteins E, pubmed-meshheading:11476599-Cues, pubmed-meshheading:11476599-Emotions, pubmed-meshheading:11476599-Escape Reaction, pubmed-meshheading:11476599-Glial Fibrillary Acidic Protein, pubmed-meshheading:11476599-Humans, pubmed-meshheading:11476599-Learning, pubmed-meshheading:11476599-Male, pubmed-meshheading:11476599-Memory Disorders, pubmed-meshheading:11476599-Mice, pubmed-meshheading:11476599-Mice, Inbred C57BL, pubmed-meshheading:11476599-Mice, Knockout, pubmed-meshheading:11476599-Mice, Transgenic, pubmed-meshheading:11476599-Motor Activity, pubmed-meshheading:11476599-Phenotype, pubmed-meshheading:11476599-Promoter Regions, Genetic, pubmed-meshheading:11476599-Reaction Time, pubmed-meshheading:11476599-Space Perception, pubmed-meshheading:11476599-Startle Reaction, pubmed-meshheading:11476599-Time Factors
pubmed:year
2001
pubmed:articleTitle
Behavioral phenotyping of GFAP-apoE3 and -apoE4 transgenic mice: apoE4 mice show profound working memory impairments in the absence of Alzheimer's-like neuropathology.
pubmed:affiliation
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't