As we have noted the Nrf2 regulates a number of genes including those that are important for mitochondrial biogenesis and other homeostatic functions and the expression of it can be effected by age, injury, oxidative stress, nutrition and other behavioral factors. As Dhar shows, the NRF-1 transcription factor upregulated by Nrf2 and important for PGC-1a activation and mitochondrial biogenesis has been shown to co-regulate a number of different genes including that for NR1, NR2b and Cox1. The Nr2b is a subunit of the NMDA which has been implicated in nociception of MCS upon upregulation (Pall) as well as, has been implicated in having involvement in other environmental illnesses including fibromyalgia. Its involvement also provides important implications for conditions of learning and cognitive difficulties that usually are co-morbid with these conditions. There does seem to be some debate on whether NMDA is upregulated or down-regulated and it may be that specific situations influence this. Yonden previously demonstrated that the downregulation of the NR2b receptor occurs with addition of experimental ammonia and concluded that downregulation of the NMDA contributes to severity of hepatic encephalopathy. This also supports our opinion that Nrf2 may influence environmental conditions including MCS and others because it is important for regulation of NRF1. It also provides supporting evidence that other health conditions where mitochondrial dysfunction is a factor, may also be influenced by the expression of Nrf2 because NRF1's role in mitochondrial biogenesis.
HEIRS Tags: NR2B, NRF1, hyperammonia,
For Further Reading: Nrf2, Ornithine Transferase, Autism and Maternal Age -- A Possible Link?
CiteULike: Coupling of Energy Metabolism and Synaptic Transmission at the Transcriptional Level: Role of Nuclear Respiratory Factor 1 in Regulating both Cytochrome c Oxidase and NMDA Glutamate Receptor Subunit Genes: "Dhar, S. S. and Wong-Riley, M. T. T. (2009). Coupling of energy metabolism and synaptic transmission at the transcriptional level: Role of nuclear respiratory factor 1 in regulating both cytochrome c oxidase and nmda glutamate receptor subunit genes. J. Neurosci., 29(2):483-492."
Yonden, Z., Aydin, M., Kilbas, A., Demirin, H., Sutcu, R., and Delibas, N. (2010). Effects of ammonia and allopurinol on rat hippocampal nmda receptors. Cell biochemistry and function. http://www.citeulike.org/user/HEIRS/article/6567065
Pall, Martin. (2007). Explaining Ünexplained Illnesses": disease paradigm for chronic fatigue syndrome, multiple chemical sensitivity, fibromyalgia, post-traumatic syndrome, Gulf War syndrome, and others. Harrington Park Press:Hawthorne Press, 10 Alice Street Binghampton NY 13904. http://www.citeulike.org/user/HEIRS/article/3042479
An older study suggests that blocking NR2B transmission results in alterations of BDNF. Recent studies show elevated levels of BDNF in fibromyalgia and at specific times in PTSD.
ReplyDeleteCrozier, R. A., Black, I. B., and Plummer, M. R. (1999). Blockade of nr2b-containing nmda receptors prevents bdnf enhancement of glutamatergic transmission in hippocampal neurons. Learning & Memory, 6(3):257-266.