Studies of the effects of central administration of beta-amyloid peptide (25-35): pathomorphological changes in the Hippocampus and impairment of spatial memory.

The possible link between amnesia induced by central administration of beta-amyloid (25-35) (Abeta(25-35)) and neurodegenerative changes in the hippocampus was studied. Male Wistar rats received single intracerebroventricular injections of Abeta(25-35) at a dose of 15 nmoles and one month later were trained in an eight-arm radial maze. Training was followed by histological assessment of the state of the hippocampus on brain sections stained with hematoxylin and eosin. Abeta(25-35) induced impairments in long-term (reference) and working memory on testing in the maze. There was a moderate reduction in the number of neurons in hippocampal field CA1; there was no change in the number of cells in field CA3. The numbers of errors made by the animals on testing in the maze were found to correlate negatively with the numbers of nerve cells in hippocampal field CA1. Thus, this is the first demonstration that impairments of learning and memory induced by single doses of Abeta(25-35) are specifically associated with neurodegenerative changes in hippocampal field CA1 in rats.