Axotomy of the sciatic nerve differentially affects expression of metabotropic glutamate receptor mRNA in adult rat motoneurons

Previous studies indicated that axotomy exposes motoneurons to glutamatergi c excitotoxic stress and protection from glutamatergic overactivation might be crucial for survival. Depending on the experimental model and the subty pe involved, activation of metabotropic glutamate receptors (mGluRs) may ei ther enhance excitotoxicity or exert protective effects. To investigate a p ossible involvement of mGluRs in neuronal rescue mechanisms after axotomy w e have monitored the distribution of mGluR mRNA with in situ hybridization in adult rat motoneurons 1, 2, 3, and 4 weeks after sciatic nerve transecti on. Motoneurons in sham-operated control animals expressed mGluR 1, 4, and 7 mRNA. The mGluR1 mRNA signal was reduced to 49.6+/-6.9% as compared to th e contralateral side 2 weeks after axotomy and 31.2+/-8.3% after 4 weeks. T he mGluR4 signal declined to 22.1+/-5.1% after 1 week and 10.2+/-1.6% after 2 weeks, remaining stable thereafter. During the entire observation period the mRNA for mGluR7 was not significantly altered. Axotomy did not change the overall number of motoneurons on the ipsi- or contralateral side. The d ifferential regulation of mGluR subtypes may be part of an adaptive cell pr ogram that helps to rescue adult motoneurons from excitotoxic cell death du ring the stress induced by peripheral denervation. (C) 2000 Elsevier Scienc e B.V. All rights reserved.