Increased beta-amyloid precursor protein mRNA in the rat cerebral cortex and hippocampus after chronic systemic...

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.