Altered expression of amyloid protein precursor mRNA in the rat hippocampus following trimethyltin intoxication: an in situ hybridization study.
Previous studies have reported increased levels of amyloid protein precursor (APP) and APP mRNA in the hippocampus and basal forebrain of patients with Alzheimer's disease. Similar changes have been found in the brains of aged rodents and transgenic mice. It now appears that alterations 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 (TMT) (8 mg/kg i.p.) on APP-751 and APP-695 mRNA expression in the rat hippocampus (CA1, CA2, CA3 and CA4) using in situ hybridization techniques. We found that following TMT treatment the expression of APP-751 mRNA was increased in CA1 pyramidal cells while that of APP-695 mRNA remained unchanged. TMT also increased the numbers of APP-751 and APP-695 mRNA positively hybridized cells in the CA1 pyramidal layer. These findings suggest that an alteration in APP mRNA expression is involved in the response of the rodent brain to TMT intoxication.
O'Connell
A W
AW
Pharmacology Department, University College, Galway, Ireland. Laois@ollamh.ucd.ie
Strada
O
O
Earley
B
B
Leonard
B E
BE
D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010446:Peptide Fragments / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014298:Trimethyltin Compounds / Q000633:toxicity*
D016564:Amyloid beta-Protein Precursor; D016376:Oligonucleotides, Antisense; D010446:Peptide Fragments; D012333:RNA, Messenger; D014298:Trimethyltin Compounds; C093599:amyloid beta-protein precursor 770 (681-695); C046488:trimethyltin