INTRAHIPPOCAMPAL INJECTIONS OF THE BETA-AMYLOID-1-28 FRAGMENT INDUCESBEHAVIORAL DEFICITS IN RATS

beta-amyloid (beta A) deposition is a key event in the etiopathogenesi s of Alzheimer's disease (AD), contributing to neuronal degeneration a nd cognitive impairment in AD patients. Both neurotrophic and neurotox ic actions of beta A have been demonstrated in experimental conditions . In order to further characterize the effects of brain beta A deposit s on behavioral processes, we evaluated psychomotor activity (PMA), ps ychomotor coordination (PMC) and learning in a passive avoidance task (PAL) in rats with unilateral or bilateral 2 mu l injections of beta-a myloid (1-28) protein (beta A; 1.5 nmol/mu l) or vehicle (water; W) in to the hippocampus, 1 and 4 weeks after neurosurgery. The extent of ne uronal loss in the lateral blade of the gyrus dentatus (LBGD) and the area percentage occupied by APP immunoreactivity in neurons of the CA3 c subfield of the hippocampus were also measured in animals with unila teral beta A implants. PMA levels were similar in water- and beta A-in jected animals 1 and 4 weeks after recovery. As compared to water-inje cted rats, beta A animals showed reduced PMC values 1 week, but not 4 weeks, after injections. beta A also impaired learning acquisition in a passive avoidance task, reducing the number of avoidances and mean l atency per trial at both 1 and 4 weeks postsurgery in rats with unilat eral or bilateral beta A implants. The extent of neuronal loss in the LBGD was not different in rats receiving water or beta A injections. H ippocampal APP expression tended to increase in beta A-implanted rats and showed a negative correlation with cognitive performance at the 4- week period. According to these results it seems that beta A implants into the hippocampus reduce psychomotor coordination performance in a transient manner, with no effect on psychomotor activity, and induce d urable learning impairment in rats, and that changes in cognitive perf ormance correlate with histochemical parameters such as APP expression . In conclusion, the present results contribute to a better understand ing of beta A-induced behavioral alterations and to the identification of potential molecular mechanisms involved in cognitive dysfunctions in this animal model of neurodegeneration.