Abeta(1-42) injection causes memory impairment, lowered cortical and serum BDNF levels, and decreased hippocampal 5-HT(2A) levels

Aggregation of the beta-amyloid protein (Abeta) is a hallmark of Alzheimer's disease (AD) and is believed to be causally involved in a neurodegenerative cascade. In patients with AD, reduced levels of serum Brain Derived Neurotrophic Factor (BDNF) and cortical 5-HT(2A) receptor binding has rece...

Full description

Saved in:
Bibliographic Details
Published in:Experimental neurology 2008-03, Vol.210 (1), p.164
Main Authors: Christensen, R, Marcussen, A B, Wörtwein, G, Knudsen, G M, Aznar, S
Format: Article
Language:English
Subjects:
Amyloid beta-Peptides
Analysis of Variance
Animals
Behavior, Animal - drug effects
Brain-Derived Neurotrophic Factor - metabolism
Cerebral Cortex - metabolism
Enzyme-Linked Immunosorbent Assay - methods
Gene Expression Regulation - drug effects
Hippocampus - drug effects
Male
Memory Disorders - chemically induced
Memory Disorders - metabolism
Memory Disorders - pathology
Memory Disorders - physiopathology
Neuropsychological Tests
Peptide Fragments
Rats
Rats, Wistar
Receptor, Serotonin, 5-HT2A - metabolism
Social Behavior
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aggregation of the beta-amyloid protein (Abeta) is a hallmark of Alzheimer's disease (AD) and is believed to be causally involved in a neurodegenerative cascade. In patients with AD, reduced levels of serum Brain Derived Neurotrophic Factor (BDNF) and cortical 5-HT(2A) receptor binding has recently been reported but it is unknown how these changes are related to beta-amyloid accumulation. In this study we examined in rats the effect of intrahippocampal injections of aggregated Abeta(1-42) (1 microg/microl) on serum and brain BDNF or 5-HT(2A) receptor levels. A social recognition test paradigm was used to monitor Abeta(1-42) induced memory impairment. Memory impairment was seen 22 days after injection of Abeta(1-42) in the experimental group and until termination of the experiments. In the Abeta(1-42) injected animals we saw an abolished increase in serum BDNF levels that was accompanied by significant lower BDNF levels in frontal cortex and by an 8.5% reduction in hippocampal 5-HT(2A) receptor levels. A tendency towards lowered cortical 5-HT(2A) was also observed. These results indicate that the Abeta(1-42) associated memory deficit is associated with an impaired BDNF regulation, which is reflected in lower cortical BDNF levels, and changes in hippocampal 5-HT(2A) receptor levels. This suggests that the BDNF and 5-HT2A changes observed in AD are related to the presence of Abeta(1-42) deposits.
ISSN:0014-4886