Transient down-regulation of NMDA receptor subunit gene expression in the rat retina following NMDA-induced neurotoxicity is attenuated in the presence of the non-competitive NMDA receptor antagonist MK-801

Experimental Eye Research
Dennis J Goebel, M S Poosch

Abstract

Excitotoxic challenge has been thought to directly target NMDA-receptive neurons to undergo cell death. Recent evidence suggests that NMDA induced cell death is a selective process and that the specificity may be determined by the subunit composition of the NMDA receptor. Using a rat retinal model, we examined the effects of NMDA induced neurotoxicity on the regulation of NMDA receptor subunit gene and protein expression levels to determine if excitotoxic challenge preferentially regulates one or more of the NMDA receptor subunits. Following NMDA insult, the mRNA levels for NR1(com ), NR2A, NR2B and, to a lesser extent, the NR2C subunit were substantially reduced within 24 hr post-treatment (PT), and remained depressed for up to 48 hr. Levels for NR2D, although initially suppressed as early as 6 hr-PT, were least affected by NMDA insult and showed almost full recovery by 48 hr. By 10 days, the levels of gene expression for all five subunits recovered to levels that were indistinguishable from sham treated and untreated retinas. Co-administration of MK-801 with NMDA suppressed the effects of NMDA-induced down-regulation of all five genes. Protein levels for NR1(com ), NR2A and NR2B were also monitored at select time points follo...Continue Reading

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Citations

Mar 6, 2012·Acta histochemica·Lily Alexandrova Vitanova
Jun 11, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Esther ShohamiYoel Kloog
Mar 3, 2004·Annals of the New York Academy of Sciences·P GuarneriR Guarneri
Aug 31, 2007·The Journal of Comparative Neurology·Daniel SunMichael Kalloniatis
Mar 8, 2013·Clinical & Experimental Optometry : Journal of the Australian Optometrical Association·Michael KalloniatisNiru Arunthavasothy
Aug 16, 2005·Neurochemistry International·W E Bitar AlatorreC Beas Zarate
Jul 12, 2019·Frontiers in Cellular Neuroscience·Shuchao WangKun Xiong
Jan 18, 2003·Brain Research. Molecular Brain Research·Aicha LaabichNigel G F Cooper

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