Comparative studies on beta amyloid deposition and brain aging

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We first investigated total gene expressions in the canine brain using a microarray system. Genes upregulated were GFAP, CNPase and p35, and those downregulated were APP and Tau.Activities "and expressions of neprilysin (Nep) and depositions of beta amyloid (A beta) were examined in the canine and feline brains. Nep was weakly expressed in the cerebral cortex and strongly in the striatum and substantia nigra (SN) in both animals. Activities of Nep were higher in the order of striatum > cerebral cortex > white matter / hippocampus. Nep activity and expression were not related to aging, although Nep activity was tended to decrease in the canine striatum with age. A beta deposition was increased with age in both dogs and cats.Strain difference of the neuronal cell loss was investigated in MPTP-treated C57BL/6 mice which is a Parkinson's disease model. Tyrosine hydroxylase (TH) expression in the SN-striatum was decreased in C57BL/6 mice but not in BALB/c mice. Some mice showed such decrease of HT expression in non-inbred ICR mice. It was therefore suggested that a single gene would be involved in the expression of the disease in the MPTP-treated Parkinson model mice.Fusion protein of green fluorescent protein (GFP) and A beta has been massively produced. The GFP-A beta was administered orally into juvenile mice and cows before or after weaning. GFP-A beta reached to the jejunum and ileum without degradation in the stomach, and incorporated through the absorptive epithelium in the villi of both species. The incorporation occurred in the suckling period. This experimental system would be an excellent model to investigate the intestinal invasion of prion protein.