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 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.
Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
R
R
Christensen
A B
AB
Marcussen
G
G
Wörtwein
G M
GM
Knudsen
S
S
Aznar
D016229:Amyloid beta-Peptides; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009483:Neuropsychological Tests; D010446:Peptide Fragments; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012919:Social Behavior
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; D044402:Receptor, Serotonin, 5-HT2A; C075222:amyloid beta-protein (1-42)