Upregulation of NMDARI mRNA induced by MK-801 is associated with massive death of axotomized motor neurones in adult rats

Neurobiology of Disease
C A SannerW D Snider

Abstract

Studies on the pathogenesis of human motor neurone disease have suffered from the absence of models of motor neurone degeneration in adult animals. Normally in adult rodents, transection of motor neurone axons results in only a modest degree of neuronal death. We reasoned that axotomy-induced motor neurone death might be enhanced by modulating glutamatergic transmission. By axotomizing the facial nerve in adult rats and then administering MK-801 for the first week of a 4-week or 8-week post-lesion survival period, we induced a 67% motor neurone loss by 8 weeks as compared with a 19% loss in controls. A possible explanation for the increased motor neurone loss after MK-801 treatment is that transient blockade of NMDA receptors may upregulate synthesis of NMDA receptor components. In order to test this idea, we employed quantitative in situ hybridization to determine the response of NMDAR1 mRNA to axotomy and axotomy + MK-801 treatment. Quantification of the percentage of area occupied by NMDAR1 silver grains per motor neurone somata indicated that axotomy alone did not provoke a change in NMDAR1 mRNA. However, axotomy and MK-801 combined treatment resulted in a highly significant upregulation of NMDAR1 mRNA when compared with co...Continue Reading

Citations

Apr 29, 2005·Brain Research. Molecular Brain Research·Isabelle VassiasCatherine de Waele
Jun 15, 2000·Journal of Neurochemistry·S D GrossmanJ R Wrathall
Apr 8, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Michal Schwartz
Oct 3, 2001·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·M Schwartz

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