Synaptic terminal degeneration and remodeling at the rat neuromuscular junction resulting from a single exposure to acrylamide.
Repetitive exposure to low doses of acrylamide results in extensive pathological changes at the neuromuscular junction (NMJ), but it remains undetermined if a single exposure to a larger dose will produce a similar neuropathological outcome. In the present study, morphometric and ultrastructural analyses of rat soleus NMJ were performed to determine early pathological effects of an intraperitoneal injection of 100 mg/kg acrylamide. Widespread nerve terminal degeneration, terminal sprouting, and endplate lengthening were evident as early as 4 days after injection. Degenerating terminal branches were swollen and exhibited enhanced argyrophilia. Ultrastructurally, the majority of terminals exhibited axolemmal abnormalities, neurofilament accumulations, and a paucity of synaptic vesicles; occasional swollen terminals lacked neurofilaments but contained increased numbers of tubulovesicular profiles. This early morphological pattern of nerve terminal changes suggests that acrylamide may disrupt both synaptic vesicle recycling and neurofilament degradation. These findings indicate that a single high dose of acrylamide triggers pathological lesions and remodeling in motor nerve terminals virtually identical to those resulting from multiple low doses.
DeGrandchamp
R L
RL
Department of Pharmacology and Toxicology, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855-0789.
Reuhl
K R
KR
Lowndes
H E
HE
D020106:Acrylamide; D000178:Acrylamides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D008297:Male; D009132:Muscles / Q000033:anatomy & histology; D009410:Nerve Degeneration / Q000187:drug effects*; D009411:Nerve Endings / Q000187:drug effects / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000033:anatomy & histology / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects; D013997:Time Factors
D000178:Acrylamides; D020106:Acrylamide