Neurotrophic regulation of mouse muscle β‐amyloid protein precursor and α₁‐antichymotrypsin as revealed by axotomy

Kunitz‐inhibitor containing forms of the β‐amyloid precursor protein (βAPP), known also as protease nexin II (PNII), and α₁‐antichymotrypsin (α₁‐ACT), a serpin, are important components of the serine protease and inhibitor balance in many tissues. In the nervous system, this balance may have trophic or growth factor activity at different stages of development, after injury and in disease states. In the current study, using immunocytochemistry and Western blotting with antibodies against the human homologues, we analyzed whether denervation affected the localization of βAPP and α₁‐ACT in adult mouse muscle following axotomy. In mouse muscle, antitive band and anti‐human βAPP antibody a band at 92 kD in both normal and denervated extracts. βAPP was present in normal mouse muscle at both neuromuscular junctions and within intramuscular nerves. α₁‐ACT was also detected at neuromuscular junctions, on the perineruim and endothelial cell surfaces. Following axotomy, both βAPP and α₁‐ACT disappeared from intramuscular nerves simultaneously. However, at the neuromuscular junction, α₁‐ACT decreased more rapidly with βAPP lingering before disappearing. Since both α₁‐ACT as well as βAPP are present within senile plaques in Alzheimer's disease brains such experiments with the nicotinic, cholinergic neuromuscular synapse in denervated muscle may help to focus experiments on the mechanism of synapse loss as well as plaque deposition in this disease. © 1994 John Wiley & Sons, Inc.