Glutamate enhances phosphorylation of neurofilaments in cerebellar granulecell culture

In amyotrophic lateral sclerosis (ALS), an abnormal increase of glutamate i n the central nervous system indicates that it may play a key role in motor neuron death. The neuronal accumulation of phosphorylated neurofilaments ( NFs) suggests an alteration of phosphorylation of NFs is also involved. Rat cerebellar granule cells (CGCs) are sensitive to glutamate neurotoxicity a nd provide a suitable model system for clarifying its mechanisms. Using cul tured CGCs, we investigated the relationship between glutamate neurotoxicit y and the phosphorylation of NFs. Because glutamate showed a dose-dependent neurotoxicity for CGCs, we adopted a 10 mu M glutamate treatment, which pr oduced no acute neurotoxicity during the experiments. The number of phospho rylated heavy subunits of neurofilaments (NF-Hs) increased to approximately twice that of the control after 72 h, although the total number of NF-Hs r emained constant throughout the experiment. The phosphorylation of NF-Hs wa s significantly suppressed by the AMPA-receptor antagonist CNQX, but not by the NMDA-receptor antagonist MK-801. Our findings therefore suggest that e xposure to a low concentration of glutamate enhances the phosphorylation of NF-Hs, mainly via the AMPA receptor. (C) 1999 Elsevier Science B.V. All ri ghts reserved.