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

• Published in: Experimental neurology 2008-03, Vol.210 (1), p.164-171
• Main Authors: Christensen, R, Marcussen, AB, Woertwein, G, Knudsen, G M, Aznar, S
• Format: Article
• Language: English
• ISSN: 0014-4886
• DOI: 10.1016/j.expneurol.2007.10.009

Aggregation of the beta-amyloid protein (A beta ) 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 sub(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 A beta sub((1-42)) (1 mu g/ mu l) on serum and brain BDNF or 5-HT sub(2A) receptor levels. A social recognition test paradigm was used to monitor A beta sub((1-42)) induced memory impairment. Memory impairment was seen 22 days after injection of A beta sub((1-42)) in the experimental group and until termination of the experiments. In the A beta sub((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 sub(2A) receptor levels. A tendency towards lowered cortical 5-HT sub(2A) was also observed. These results indicate that the A beta sub((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 sub(2A) receptor levels. This suggests that the BDNF and 5-HT2A changes observed in AD are related to the presence of A beta sub((1-42)) deposits.