Selective vulnerability of spinal cord motor neurons to non-NMDA toxicity

We previously reported that alpha-motor neurons in organotypic cultures of rat spinal cord (OTC-SC) are resistant to excitotoxicity induced through NM DA receptors. Here we describe the effects of non-NMDA glutamate receptor a gonists kainic acid (KA) and quisqualic acid (QUIS) on motor neurons in OTC -SC. Large ventral horn acetylcholinesterase-positive neurons (VHANs), most of which are motor neurons, were quite sensitive to QUIS and KA toxicity a nd displayed losses of 95% and 94%, respectively. Small VHANs were reduced by 41% and 61% only. Identical results were obtained in cultures stained fo r non-phosphorylated neurofilaments. These observations demonstrate that a- motor neurons are considerably more sensitive to KA and QUIS than to NMDA t oxicity. The proposed excitotoxic mechanism of ALS, therefore, is most like ly mediated through non-NMDA glutamate receptors. NeuroReport 11:1117-1121 (C) 2000 Lippincott Williams & Wilkins.