GLYCINE EFFECTS ON GLUTAMATE-RECEPTOR ELICITED ACETYLCHOLINESTERASE RELEASE FROM SLICES AND SYNAPTOSOMES OF THE SPINAL VENTRAL HORN

To study the mechanisms by which glutamate-elicited acetylcholinestera se release (GEAR) might play a part in the pathogenesis of excitotoxic ally triggered motor neurone disease, and to investigate the interacti on of GEAR with spinal glycinergic mechanisms, we measured acetylcholi nesterase (AChE) and cholinergic markers, after stimulating ventral ho rn slices and synaptosomes from the mouse spinal cord, with both gluta mate- and glycine-receptor agonists. Glutamate (GLU), kainate and AMPA , as well as glycine (GLY)evoked dose-related, calcium-dependent liber ation of soluble forms of AChE from both slices and synaptosomes. GLY- evoked AChE release showed remarkable age-related postnatal changes. I n the immature slice of the ventral hem, GLY potentiated the GEAR resp onse in the presence of strychnine, suggesting N-methyl-D-aspartate (N MDA) receptor involvement, and was also able to evoke a strychnine-sen sitive AChE release in the abscence of exogenous GLU. After the 28th p ostnatal day, nearly all the AChE secreted was released either after t he activation of non-NMDA glutamate receptors or by strychnine-sensiti ve GLY-evoked AChE release mechanisms. Both GEAR and GLY-evoked AChE r elease might impair the negative feedback loop which modulates the ove ractivation of motor neurones, and cause prolonged extracellular rises of soluble AChE. These effects might augment the vulnerability of mot or neurones to excitotoxic stress, promote fiber outgrowth, and eventu ally accelerate the metabolic exhaustion of lower motor neurones. It i s possible that the mechanisms described are operative at the spinal c ord of ALS/MND patients.