ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS DELAYS APOPTOSIS OF CHICK EMBRYONIC MOTOR-NEURONS IN-VITRO

GLUTAMATERGIC excitotoxicity has been implicated in the pathogenesis o f amyotrophic lateral sclerosis (ALS). However, activation of metabotr opic glutamate receptors (mGluRs) is neuroprotective in several paradi gms. We therefore tested the effect of selective mGluR agonists on cul tured chick embryonic motor neurons. Activation of group I mGluRs with (s)-3,5-dihydroxyphenylglycine (DHPG) and group III mGluRs with L-2-a mino-4-phosphono-butanoate (L-AP4) promoted a modest but significant, dose-dependent delay of apoptosis, which could be blocked by specific mGluR antagonists. Group II or selective mGluR5 stimulations were inef fective. Correspondingly, in situ hybridization experiments showed onl y expression of mGluR1 (group I) and mGluR4 and 7 (group III) in human motor neurons. Dissection of the pathways involved in this survival e ffect may help to elucidate the pathogenesis of ALS. (C) 1998 Rapid Sc ience Ltd.