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

TY - JOUR

T1 - Abeta(1-42) injection causes memory impairment, lowered cortical and serum BDNF levels, and decreased hippocampal 5-HT(2A) levels

AU - Christensen, R

AU - Marcussen, Anders Bue

AU - Wörtwein, Gitta

AU - Knudsen, G M

AU - Aznar, S

N1 - Keywords: Amyloid beta-Protein; Analysis of Variance; Animals; Behavior, Animal; Brain-Derived Neurotrophic Factor; Cerebral Cortex; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Hippocampus; Male; Memory Disorders; Neuropsychological Tests; Peptide Fragments; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2A; Social Behavior

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1016/j.expneurol.2007.10.009

DO - 10.1016/j.expneurol.2007.10.009

M3 - Journal article

C2 - 18053988

SN - 0014-4886

VL - 210

SP - 164

EP - 171

JO - Experimental Neurology

JF - Experimental Neurology

IS - 1

ER -