Anneser J M, Berthele A, Borasio G D, Castro-Lopes J M, Zieglgänsberger W, Tölle T R
Clinical Neuropharmacology, Max-Planck Institute of Psychiatry, Kraepelinstr. 2, 80804, München, Germany.
Brain Res. 2000 Jun 23;868(2):215-21. doi: 10.1016/s0006-8993(00)02332-5.
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.
先前的研究表明,轴突切断术使运动神经元暴露于谷氨酸能兴奋性毒性应激之下,而免受谷氨酸能过度激活的保护作用可能对其存活至关重要。根据实验模型和所涉及的亚型,代谢型谷氨酸受体(mGluRs)的激活可能会增强兴奋性毒性或发挥保护作用。为了研究mGluRs在轴突切断术后神经元拯救机制中可能的作用,我们在坐骨神经横断后1、2、3和4周,通过原位杂交监测了成年大鼠运动神经元中mGluR mRNA的分布。假手术对照动物的运动神经元表达mGluR 1、4和7 mRNA。轴突切断术后2周,mGluR1 mRNA信号与对侧相比降低至49.6±6.9%,4周后降至31.2±8.3%。mGluR4信号在1周后降至22.1±5.1%,2周后降至10.2±1.6%,此后保持稳定。在整个观察期内,mGluR7的mRNA没有明显变化。轴突切断术并未改变同侧或对侧运动神经元的总数。mGluR亚型的差异调节可能是适应性细胞程序的一部分,有助于在周围神经去神经支配诱导的应激过程中,将成年运动神经元从兴奋性毒性细胞死亡中拯救出来。