Ammonia, ASIC Channels and Mental Health

We recently have been discussing how the biological accumulation of ammonia may be an important condition related to a number of environmental illnesses. In fact, several studies suggest that accumulation of ammonia may contribute to autism and others note it plays a very important role in hepatic failure. As we noted, elevated levels of homocysteinemia may impair the urea cycle - which helps the body get rid of excess ammonia and glutamine synthetase genes of the Wnt/Catenin pathway, also regulate  ammonia concentrations in the body. Interestingly, several "so-called therapies" for MCS also have the capacity to reduce ammonia. Also, it is well-known that psychological disturbances are co-morbid with a number of environmental conditions, in addition to those mental effects associated with autism and liver disease.

In light of the potential for elevated ammonia levels to influence the psychological and physical effects of environmental disease, I thought I would point out two interesting studies. The first is a study that suggests that ASIC channels contribute to the health consequences where hyperammonemia becomes an issue. As the author points out, this may include hepatic encephalopathy, cirrhosis and neuronal disorders. This study discusses how these types of channels have been implicated in neuronal death after their activation. Incidentally, nociceptive behavior is associated with acidic environments that develop from injury and inflammation and therefore could play a role in the pain generation in environmental illnesses including  MCS (Pall) and chronic fatigue syndrome (Light).  Pidoplichko provides evidence the involvement of these channels may contribute to the loss of dopamine neurons in Parkinson's disease because these channels are associated with those neurons and "ammonium sensitivity is a widely distributed ASIC characteristic in the CNS, including the hippocampus." The second study seems to suggest that these same channels have an important role in the development of depression-related behavior by demonstrating genetically altered -/- mice presented with anti-depressant-like behaviors even while put under experiemental stress. In addition, the dysruption of these channels interfered with an important "biomarker of depression" which is a decrease of levels of BDNF in the hippocampus. In past blogs, we have explained how BDNF is important for "olfactory neurogenesis" and may be important consideration in the development of MCS.  Coryell concludes by saying that his "findings of ASIC1 signaling in the amydala in mood regulation support others and that pharmaceutical approaches that target ASIC1 signaling may be therapeutic for this kind of depression. We might propose that investigating therapies that reduce ASIC signaling may be beneficial for a number of environmentally-related conditions may be of value.

Notes:

• A recent study shows that HO-1 activates bilirubin and CO to modulate BDNF/GDNF in neurons and astrocytes. This provides a protective effect on dopaminergic neurons.

Coryell, M. W., Wunsch, A. M., Haenfler, J. M., Allen, J. E., Schnizler, M., Ziemann, A. E., Cook, M. N., Dunning, J. P., Price, M. P., Rainier, J. D., Liu, Z., Light, A. R., Langbehn, D. R., and Wemmie, J. A. (2009). Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior. J. Neurosci., 29(17):5381-5388. http://www.citeulike.org/user/HEIRS/article/6607146
Pidoplichko, V. I. and Dani, J. A. (2006). Acid-sensitive ionic channels in midbrain dopamine neurons are sensitive to ammonium, which may contribute to hyperammonemia damage. Proceedings of the National Academy of Sciences of the United States of America, 103(30):11376-11380. http://www.citeulike.org/user/HEIRS/article/6607127
Light, A. R., White, A. T., Hughen, R. W., and Light, K. C. (2009). Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. The journal of pain : official journal of the American Pain Society. http://www.citeulike.org/user/HEIRS/article/5370052
Ugawa, S., Ueda, T., Ishida, Y., Nishigaki, M., Shibata, Y., and Shimada, S. (2002). Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors. The Journal of clinical investigation, 110(8):1185-1190. http://www.citeulike.org/user/HEIRS/article/2942104
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
Hung, S.-Y. Y., Liou, H.-C. C., and Fu, W.-M. M. (2010). The mechanism of heme oxygenase-1 action involved in the enhancement of neurotrophic factor expression. Neuropharmacology, 58(2):321-329. http://www.citeulike.org/user/HEIRS/article/6196852