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 f ollowing chronic intracerebroventricular infusion of beta-amyloid (1-40) in rats. beta-amyloid was either infused intermittently via implanted cannula e on the day of operation and subsequently on postsurgical days 4, 7, 10, a nd 13 (Experiment 1), or continuously using osmotic pumps for 14 days (Expe riment 2). The same amount of beta-amyloid was delivered under both infusio n regimes. In both experiments, beta-amyloid infusion led to severe deficit s in the acquisition of a spatial reference memory task conducted on postop erative days 10 to 14, The animals were sacrificed on the postoperative day 15 for neurochemical analyses. These included radioenzymatic and radioimmu noassays, 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 prot ection assay for preprosomatostatin mRNA quantification, There was a signif icant reduction in choline acetyltransferase activity and in the levels of substance P as well as somatostatin and preprosomatostatin mRNA in the cort ical mantle of beta-amyloid-treated rats, compared to controls in both expe riments, Appreciable reductions in choline acetyltransferase activity and s omatostatin level were also apparent in the hippocampus, In contrast, beta- amyloid infusion did not significantly affect the brain level of neuropepti de 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. (C) 1999 Elsevier Science Inc.