title: Excitotoxic motoneuron disease in chick embryo evolves with autophagic neurodegeneration and deregulation of neuromuscular innervation.
abstract: In the chick embryo, in ovo application of NMDA from embryonic day (E) 5 to E9 results in selective damage to spinal cord motoneurons (MNs) that undergo a long-lasting degenerative process without immediate cell death. This contrasts with a single application of NMDA on E8, or later, which induces massive necrosis of the whole spinal cord. Chronic MN degeneration after NMDA implies transient incompetence to develop programmed cell death, altered protein processing within secretory pathways, and late activation of autophagy. Chronic NMDA treatment also results in an enlargement of thapsigargin-sensitive Ca(2+) stores. In particular MN pools, such as sartorius-innervating MNs, the neuropeptide CGRP is accumulated in somas, peripheral axons and neuromuscular junctions after chronic NMDA treatment, but not in embryos paralyzed by chronic administration of curare. Intramuscular axonal branching is also altered severely after NMDA: it usually increases, but in some cases a marked reduction can also be observed. Moreover, innervated muscle postsynaptic sites increase by NMDA, but to a lesser extent than by curare. Because some of these results show interesting homologies with MN pathology in human sporadic ALS, the model presented here provides a valuable tool for advancing in the understanding of some cellular and molecular processes particularly involved in this disease.
authors.affiliation: Unitat de Neurobiologia Cellular, Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Catalonia, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Calderó
authors.forename: Olga
authors.initials: O
authors.lastname: Tarabal
authors.forename: Anna
authors.initials: A
authors.lastname: Casanovas
authors.forename: Dolors
authors.initials: D
authors.lastname: Ciutat
authors.forename: Celia
authors.initials: C
authors.lastname: Casas
authors.forename: Jerònia
authors.initials: J
authors.lastname: Lladó
authors.forename: Josep E
authors.initials: JE
authors.lastname: Esquerda
mesh_terms: D000367:Age Factors; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002642:Chick Embryo / Q000187:drug effects; D003472:Curare / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D046529:Microscopy, Electron, Transmission / Q000379:methods; D016472:Motor Neuron Disease / Q000139:chemically induced / Q000473:pathology*; D009046:Motor Neurons / Q000187:drug effects* / Q000648:ultrastructure; D016202:N-Methylaspartate / Q000494:pharmacology; D009410:Nerve Degeneration / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000473:pathology*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology; D014404:Tubulin / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D003473:Neuromuscular Nondepolarizing Agents; D011978:Receptors, Nicotinic; D014404:Tubulin; D016202:N-Methylaspartate; D003472:Curare; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium