ALTERED EXPRESSION OF AMYLOID PROTEIN-PRECURSOR MESSENGER-RNA IN THE RAT HIPPOCAMPUS FOLLOWING TRIMETHYLTIN INTOXICATION - AN IN-SITU HYBRIDIZATION STUDY

Previous studies have reported increased levels of amyloid protein pre cursor (APP) and APP mRNA in the hippocampus and basal forebrain of pa tients with Alzheimer's disease. Similar changes have been found in th e brains of aged rodents and transgenic mice. It now appears that alte rations in the expression of individual isoforms of APP mRNA may have a role to play in amyloid pathogenesis. Here we examined the effect of acute administration of the limbic system neurotoxin trimethyltin (TM T) (8 mg/kg i.p.) on APP-751 and APP-695 mRNA expression in the rat hi ppocampus (CA(1), CA(2), CA(3) and CA(4)) using in situ hybridization techniques. We found that following TMT treatment the expression of AP P-751 mRNA was increased in CA(1) pyramidal cells while that of APP-69 5 mRNA remained unchanged. TMT also increased the numbers of APP-751 a nd APP-695 mRNA positively hybridized cells in the CA(1) pyramidal lay er. These findings suggest that an alteration in APP mRNA expression i s involved in the response of the rodent brain to TMT intoxication. (C ) 1997 Elsevier Science Ltd. All rights reserved.