GLUTAMATE-RECEPTOR ELICITED ACETYLCHOLINESTERASE RELEASE IN MOUSE SPINAL-CORD SLICE - A MODEL OF EARLY EXCITOTOXIC INJURY

To investigate the mechanisms by which glutamate-induced acetylcholine sterase (AChE) release might play a part in the pathogenesis of excito toxically triggered motor neurone disease, we measured AChE molecular forms released after glutamate-receptor agonist stimulation of superfu sed and incubated slices of mouse spinal cord. Kainate and GLU caused a dose-related, calcium-dependent, magnesium-blocked liberation of ACh E soluble forms (mainly G4) from both the ventral and dorsal horns, wi thout membrane damage. In the immature slice, glycine potentiated GLU elicited AChE release in the presence of strychnine, suggesting N-meth yl-D-aspartate (NMDA) receptor involvement. After the 30th postnatal d ay, nearly all the release was caused by non-NMDA receptor stimulation . The response might interfere with the negative feedback loop which m odulates the overactivation of motor neurones, and might render them m ore vulnerable to excitotoxic stress.