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

Exp Neurol. 2008 Mar;210(1):164-71. doi: 10.1016/j.expneurol.2007.10.009. Epub 2007 Nov 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Amyloid beta-Peptides
  • Brain-Derived Neurotrophic Factor
  • Peptide Fragments
  • Receptor, Serotonin, 5-HT2A
  • amyloid beta-protein (1-42)