NEUROTROPHIC REGULATION OF MOUSE MUSCLE BETA-AMYLOID PROTEIN-PRECURSOR AND ALPHA(1)-ANTICHYMOTRYPSIN AS REVEALED BY AXOTOMY

Kunitz-inhibitor containing forms of the beta-amyloid precursor protei n (beta APP), known also as protease nexin II (PNII), and alpha(1)-ant ichymotrypsin (alpha(1)-ACT), a serpin, are important components of th e serine protease and inhibitor balance in many tissues. In the nervou s system, this balance may have trophic or growth factor activity at d ifferent stages of development, after injury and in disease states. In the current study, using immunocytochemistry and Western blotting wit h antibodies against the human homologues, we analyzed whether denerva tion affected the localization of beta APP and alpha(1)-ACT in adult m ouse muscle following axotomy. In mouse muscle, antihuman alpha(1)-ACT antibody detected a 60 kD immunoreactive band and anti-human beta APP antibody a band at 92 kD in both normal and denervated extracts. beta APP was present in normal mouse muscle at both neuromuscular junction s and within intramuscular nerves. alpha(1)-ACT was also detected at n euromuscular junctions, on the perineurium and endothelial cell surfac es. Following axotomy, both beta APP and alpha(1)-ACT disappeared from intramuscular nerves simultaneously. However, at the neuromuscular ju nction, alpha(1)-ACT decreased more rapidly with beta APP lingering be fore disappearing. Since both alpha(1)-ACT as well as beta APP are pre sent within senile plaques in Alzheimer's disease brains such experime nts with the nicotinic, cholinergic neuromuscular synapse in denervate d muscle may help to focus experiments on the mechanism of synapse los s as well as plaque deposition in this disease. (C) 1994 John Wiley an d Sons, Inc.