Glutamate-receptor elicited acetylcholinesterase release in mouse spinal cord slice: a model of early excitotoxic injury.
To investigate the mechanisms by which glutamate-induced acetylcholinesterase (AChE) release might play a part in the pathogenesis of excitotoxically triggered motor neurone disease, we measured AChE molecular forms released after glutamate-receptor agonist stimulation of superfused and incubated slices of mouse spinal cord. Kainate and GLU caused a dose-related, calcium-dependent, magnesium-blocked liberation of AChE soluble forms (mainly G4) from both the ventral and dorsal horns, without membrane damage. In the immature slice, glycine potentiated GLU elicited AChE release in the presence of strychnine, suggesting N-methyl-D-aspartate (NMDA) receptor involvement. After the 30th postnatal day, nearly all the release was caused by non-NMDA receptor stimulation. The response might interfere with the negative feedback loop which modulates the overactivation of motor neurones, and might render them more vulnerable to excitotoxic stress.
Rodríguez-Ithurralde
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D
Laboratory of Molecular Neuroscience, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay.
Olivera
S
S
Migues
V
V
Vincent
O
O
Salazar
R
R
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018698:Glutamic Acid / Q000633:toxicity*; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D013118:Spinal Cord Diseases / Q000139:chemically induced* / Q000201:enzymology*; D013331:Strychnine / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018684:Glycine Agents; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D000110:Acetylcholinesterase; D013331:Strychnine; D007608:Kainic Acid; D005998:Glycine