Increased beta-amyloid precursor protein mRNA in the rat cerebral cortex and hippocampus after chronic systemic atropine treatment.
Rats were treated with once-daily subcutaneous injections of atropine or normal saline for 10 days. Cryostat sections of fresh-frozen brain were subjected to quantitative muscarinic receptor ([3H]quinuclidinylbenzilate (QNB)) binding autoradiography, and quantitative in-situ hybridization autoradiography for beta-amyloid precursor protein (beta-APP) mRNA using an oligonucleotide probe recognizing all major isoforms. QNB binding in the atropine-treated group was increased 6-7% in the areas measured (dentate gyrus, CA1, and cerebral cortex), confirming that the treatment was effective in inducing muscarinic receptor upregulation. Hybridization signal for beta-APP mRNA was increased 15-20% in the atropine-treated group in the same regions. As chronic atropine treatment models the muscarinic effects of cholinergic denervation, these results suggest that age-related cholinergic neuron loss may result in upregulation of beta-APP.
Beach
T G
TG
University of British Columbia, Vacouver Hospital and Health Sciences Centre, Department of Pathology, Canada.
Walker
D G
DG
Cynader
M S
MS
Hughes
L H
LH
D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001345:Autoradiography; D002540:Cerebral Cortex / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D017403:In Situ Hybridization; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D018727:Muscarinic Antagonists; D012333:RNA, Messenger; D011813:Quinuclidinyl Benzilate; D001285:Atropine