Reduction in somatostatin and substance P levels and choline acetyltransferase activity in the cortex and hippocampus of the rat after chronic intracerebroventricular infusion of beta-amyloid (1-40).

The present study investigated the neurochemical and behavioural sequelae following chronic intracerebroventricular infusion of beta-amyloid (1-40) in rats. beta-amyloid was either infused intermittently via implanted cannulae on the day of operation and subsequently on postsurgical days 4, 7, 10, and 13 (Experiment 1), or continuously using osmotic pumps for 14 days (Experiment 2). The same amount of beta-amyloid was delivered under both infusion regimes. In both experiments, beta-amyloid infusion led to severe deficits in the acquisition of a spatial reference memory task conducted on postoperative days 10 to 14. The animals were sacrificed on the postoperative day 15 for neurochemical analyses. These included radioenzymatic and radioimmunoassays, designed to determine choline acetyltransferase activity and the contents of neuropeptides (somatostatin, substance P, and neuropeptide Y), respectively. Experiment 2 also included solution-hybridisation-RNAase protection assay for preprosomatostatin mRNA quantification. There was a significant reduction in choline acetyltransferase activity and in the levels of substance P as well as somatostatin and preprosomatostatin mRNA in the cortical mantle of beta-amyloid-treated rats, compared to controls in both experiments. Appreciable reductions in choline acetyltransferase activity and somatostatin level were also apparent in the hippocampus. In contrast, beta-amyloid infusion did not significantly affect the brain level of neuropeptide Y. The present study demonstrated that chronic infusion of beta-amyloid can lead to a reduction in the levels of selected neuropeptides resembling the pattern seen in Alzheimer's disease patients.