Peptide YY administration decreases brain aluminum in the Ts65Dn Down syndrome mouse model

We have previously reported the Ts65Dn (Ts) mouse has impaired intestinal a bsorptive function and amino acid metabolism. Peptide YY (PYY) has enhanced glucose absorption in mice and turkeys. Other studies have reported that p ersons with Down syndrome have increased intestinal absorption of aluminum. Alzheimer's-like lesions have been reported in Ts mice. Trial 1 of this st udy examined brain Al concentrations, plasma metabolites and intestinal met abolism of 40 control and 40 Ts mice administered 300 mu g PYY/kg body weig ht or 0.9% saline for 3d. Trial 2 examined nutrient digestibility of 12 C a nd 12 Ts given PYY or saline for 14d. In Trial 1, PW lowered (p<0.05) the b rain Al pool (mg/g FEW) in both C and Ts mice by 80% compared to saline. Ts mice had increased plasma NH3 (329 vs. 269 mu M, p<0.05), decreased plasma glucose (7.4 vs. 8.4 mM, p<0.01), elevated apparent energetic efficiency o f jejunal glucose uptake (p<0.01) and elevated brain Al pool (0.41 vs. 0.12 mu g, p=0.06) compared to C mice. In Trial 2, PYY increased small intestin al density (mg/cm) 12% in both genotypes (p<0.05), but did not alter nutrie nt digestibility. Brain Al accretion and hyperammonemia are proposed risk f actors for Alzheimer's disease (AD). Ts mice and PW appear to be suitable m odels for the study of metabolic and neurological anomalies in Down syndrom e and AD.