Differential expression of group I metabotropic glutamate receptors in ratspinal cord somatic and autonomic motoneurons: Possible implications for the pathogenesis of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder charact erized by the progressive loss of somatic, but not autonomic, motoneurons. The reason for this selective vulnerability is unknown. The pathogenesis of ALS is thought to involve glutamatergic excitotoxic mechanisms. While over activation of ionotropic glutamate receptors may trigger excitotoxicity, we have previously shown that stimulation of group I metabotropic glutamate r eceptors (mGluRs) can exert neuroprotective effects on cultured motoneurons . Using in situ hybridization, we found a differential expression of group I mGluRs (mGluR1 and 5) in rat spinal cord. Autonomic motoneurons from the sacral parasympathetic Onuf's nucleus and thoracic sympathetic neurons, whi ch are spared in ALS, express high levels of mGluR5, while somatic motoneur ons do not. In addition, mGluR1 mRNA is found only in smaller somatic moton eurons, which seem to be less vulnerable in ALS. Thus, differential mGluR e xpression might provide a possible clue to the selective vulnerability of d ifferent motoneuronal subpopulations in ALS. (C) 1999 Academic Press.