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 glutamatergic excitotoxic stress and protection from glutamatergic overactivation might be crucial for survival. Depending on the experimental model and the subtype involved, activation of metabotropic glutamate receptors (mGluRs) may either enhance excitotoxicity or exert protective effects. To investigate a possible involvement of mGluRs in neuronal rescue mechanisms after axotomy we have monitored the distribution of mGluR mRNA with in situ hybridization in adult rat motoneurons 1, 2, 3, and 4 weeks after sciatic nerve transection. 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 the contralateral side 2 weeks after axotomy and 31.2+/-8.3% after 4 weeks. The 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 differential regulation of mGluR subtypes may be part of an adaptive cell program that helps to rescue adult motoneurons from excitotoxic cell death during the stress induced by peripheral denervation.
Anneser
J M
JM
Clinical Neuropharmacology, Max-Planck Institute of Psychiatry, Kraepelinstr. 2, 80804, München, Germany. janneser@brian.nefo.med.uni-muenchen.de
Berthele
A
A
Borasio
G D
GD
Castro-Lopes
J M
JM
Zieglgänsberger
W
W
Tölle
T R
TR
D000818:Animals; D019771:Axotomy / Q000009:adverse effects*; D002452:Cell Count; D005260:Female; D009046:Motor Neurons / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*
D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; C104077:metabotropic glutamate receptor type 1; C108823:metabotropic glutamate receptor 4