title: Loss of neurofilaments in the neuromuscular junction in a rat model of proximal axonopathy.
abstract: OBJECTIVE
  Rodents exposed to 3,3'-iminodipropionitrile (IDPN) develop an axonopathy similar to that observed in amyotrophic lateral sclerosis motor neurones, in which neurofilaments accumulate in swollen proximal axon segments. This study addressed the hypotheses that this proximal axonopathy is associated with loss of neurofilament proteins in the neuromuscular junctions and a progressive loss of neurofilaments advancing in a distal-proximal direction from the distal motor nerve.
  
  
  METHODS
  Adult male Long-Evans rats were exposed to 0 or 15 mM of IDPN in drinking water for 1, 3 or 5 weeks, and their distal axons and neuromuscular junction organization studied by immunohistochemistry. Quantitative data were obtained by confocal microscopy on whole mounts of the Levator auris longus.
  
  
  RESULTS
  Muscles showed no change in the distribution of acetylcholine receptor labelling in the neuromuscular junctions after IDPN. In contrast, the amount of neurofilament labelling in the junctions was significantly reduced by IDPN, assessed with two different anti-neurofilament antibodies. In preterminal axons and in more proximal axon levels, no statistically significant reductions in neurofilament content were observed.
  
  
  CONCLUSIONS
  The proximal neurofilamentous axonopathy induced by IDPN is associated with an abnormally low content of neurofilaments in the motor terminals, with a potential impact in the function or stability of the neuromuscular junction. In contrast, neurofilaments are significantly maintained in the distal axon.
authors: Departament de Ciències Fisiològiques II, Universitat de Barcelona, Spain.
authors: C
authors: C
authors: Soler-Martín
authors: U
authors: U
authors: Vilardosa
authors: S
authors: S
authors: Saldaña-Ruíz
authors: N
authors: N
authors: Garcia
authors: J
authors: J
authors: Llorens
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D016900:Neurofilament Proteins / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity; D009570:Nitriles / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D016900:Neurofilament Proteins; D009498:Neurotoxins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile