title: Glutamate protects neuromuscular junctions from deleterious effects of β-amyloid peptide and conversely: an in vitro study in a nerve-muscle coculture.
abstract: Murine models of Alzheimer's disease with elevated levels of amyloid-β (Aβ) peptide present motor axon defects and neuronal death. Aβ1-42 accumulation is observed in motor neurons and spinal cords of sporadic and familial cases of amyotrophic lateral sclerosis (ALS). Motor neurons are highly susceptible to glutamate, which has a role in ALS neuronal degeneration. The current study investigates the link between Aβ and glutamate in this neurodegenerative process. Primary rat nerve and human muscle cocultures were intoxicated with glutamate or Aβ. Neuromuscular junction (NMJ) mean size and neurite length were evaluated. The role of N-methyl-D-aspartate receptor (NMDAR) was investigated by using MK801. Glutamate and Aβ production were evaluated in culture supernatant. The current study shows that NMJs are highly sensitive to Aβ peptide, that the toxic pathway involves glutamate and NMDAR, and that glutamate and Aβ act in an interlinked manner. Some motor diseases (e.g., ALS), therefore, could be considered from a new point of view related to these balance disturbances.
authors.affiliation: Department of Research and Development, Neuro-Sys SAS, Gardanne, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Combes
authors.forename: Philippe
authors.initials: P
authors.lastname: Poindron
authors.forename: Noelle
authors.initials: N
authors.lastname: Callizot
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D053148:Caspase 3 / Q000378:metabolism; D018920:Coculture Techniques; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D018698:Glutamic Acid / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009132:Muscles / Q000187:drug effects*; D016900:Neurofilament Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology
chemical_list: D016229:Amyloid beta-Peptides; D018690:Excitatory Amino Acid Agonists; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C051774:neurofilament protein H; D018698:Glutamic Acid; D053148:Caspase 3
keywords: ALS; NMDAR; NMJ; amyloid-β peptide; glutamate