Premium
Excitotoxic motoneuron degeneration induced by glutamate receptor agonists and mitochondrial toxins in organotypic cultures of chick embryo spinal cord
Author(s) -
Brunet Núria,
Tarabal Olga,
Esquerda Josep E.,
Calderó Jordi
Publication year - 2009
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22118
Subject(s) - excitotoxicity , riluzole , cnqx , glutamate receptor , neuroprotection , kainate receptor , biology , kainic acid , neuroscience , nmda receptor , astrogliosis , ampa receptor , microbiology and biotechnology , pharmacology , central nervous system , receptor , biochemistry
Glutamate receptor‐mediated excitotoxicity and mitochondrial dysfunction appear to play an important role in motoneuron (MN) degeneration in amyotrophic lateral sclerosis (ALS). In the present study we used an organotypic slice culture of chick embryo spinal cord to explore the responsiveness of mature MNs to different excitotoxic stimuli and mitrochondrial inhibition. We found that, in this system, MNs are highly vulnerable to excitotoxins such as glutamate, N‐methyl‐D‐aspartate (NMDA), and kainate (KA), and that the neuroprotective drug riluzole rescues MNs from KA‐mediated excitotoxic death. MNs are also sensitive to chronic mitochondrial inhibition induced by malonate and 3‐nitropropionic acid (3‐NP) in a dose‐dependent manner. MN degeneration induced by treatment with mitochondrial toxins displays structural changes similar to those seen following excitotoxicity and can be prevented by applying either the antiexcitotoxic drug 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione disodium (CNQX) or riluzole. Excitotoxicity results in an increased frequency of normal spontaneous Ca 2+ oscillations in MNs, which is followed by a sustained deregulation of intracellular Ca 2+ . Tolerance to excitotoxic MN death resulting from chronic exposure to excitotoxins correlates with a reduced excitotoxin‐induced increase in intracellular Ca 2+ and increased thapsigargin‐sensitive Ca 2+ stores. J. Comp. Neurol. 516:277–290, 2009. © 2009 Wiley‐Liss, Inc.