Activation of metabotropic glutamate receptors delays apoptosis of chick embryonic motor neurons in vitro.
Glutamatergic excitotoxicity has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, activation of metabotropic glutamate receptors (mGluRs) is neuroprotective in several paradigms. We therefore tested the effect of selective mGluR agonists on cultured chick embryonic motor neurons. Activation of group I mGluRs with (s)-3,5-dihydroxyphenylglycine (DHPG) and group III mGluRs with L-2-amino-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 ineffective. Correspondingly, in situ hybridization experiments showed only expression of mGluR1 (group I) and mGluR4 and 7 (group III) in human motor neurons. Dissection of the pathways involved in this survival effect may help to elucidate the pathogenesis of ALS.
Neurologische Klinik der Ludwig-Maximilians-Universität München, Klinikum Grosshadern, Germany.
J M
JM
Anneser
S
S
Horstmann
P
P
Weydt
G D
GD
Borasio
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006801:Humans; D017403:In Situ Hybridization; D009046:Motor Neurons / Q000187:drug effects*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate