Solvents, PAHs and BDNF as a Modulator of TrkB, Anxiety and Nrf2~!

In other blogs, we have discussed how BDNF may play important roles for neuron health and therefore, may play an important role in environmental illnesses. This neutrophic factor is an important regulator in pathways of the cell. Older studies suggest it regulates the PI3K-Nrf2 pathway and Donovan explains that BDNF-TrkB are important for hippocampal regulation. This new studies further supports the role of BDNF in anxiety disorders and possibly others like PTSD. Other studies have shown that "chronic exposure to solvents has a number of health effects including abnormal EEG's, altered sense of smell, numbness or weakness in the extremities, emotional problems, including depressive tendencies, anxiety and social withdrawal. Also, frequent associations between the sense of well being and the cognitive functioning were reported by many authors. Hegazy et al suggests that some of the symptoms related to solvent exposure may be from downregulation of protein expression including BDNF and the activation of the AhR in response to some pollutants may influence BDNF expression as well. (Lin)  This has important implications overall, for the effects of solvent use and their hazards on the modulation of the antioxidant system in general. Taking these studies into account and others in recent months, it has been suggested that modulation through pharmacological or flavonoid therapy may provides benefits and correction of this pathway and be important for neurological disorders such as Parkinson's disease.

"11 base pair deletion in TrkB is significantly associated with increases in anxiety traits during childhood and the development of anxiety disorders in adulthood. We found that this deletion impaired transcription in some human cell lines"

Read more: CiteULike: A Deletion in Tropomyosin-Related Kinase B and the Development of Human Anxiety.:

Comment: In yesterdays blog, I noted how PAH may negatively effect autism genes and becomes an important consider also!


Related Tags: neurotrophins, BDNF, Nrf2


Ernst, C., Wanner, B., Brezo, J., Vitaro, F., Tremblay, R., and Turecki, G. (2010). A Deletion in Tropomyosin-Related Kinase B and the Development of Human Anxiety. Biological psychiatry.
http://www.citeulike.org/user/HEIRS/article/8364218
Nakaso, K., Nakamura, C., Sato, H., Imamura, K., Takeshima, T., and Nakashima, K. (2006). Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins. Biochemical and biophysical research communications, 339(3):915-922. http://www.citeulike.org/user/HEIRS/article/5770676?show_msg=already_posted
Donovan, M. H., Yamaguchi, M., and Eisch, A. J. (2008). Dynamic expression of TrkB receptor protein on proliferating and maturing cells in the adult mouse dentate gyrus. Hippocampus, 18(5):435-439. http://www.citeulike.org/user/HEIRS/article/8364397
Hegazy, N. M., Abdel Gawad, N. B., Metwally, F. M., Ahmed, H. H., Abdel Raouf, E. R., Abrahim, K. S., and Sharaf, N. E. (2010). Neurotoxic effects of organic solvents in exposed workers: Altered expression of some biochemical markers. New York Science Journal, 3(11):171-176.
http://www.citeulike.org/user/HEIRS/article/8364905
Sheng, L., Ding, X., Ferguson, M., McCallister, M., Rhoades, R., Maguire, M., Ramesh, A., Aschner, M., Campbell, D., Levitt, P., and Hood, D. B. (2010). Prenatal polycyclic aromatic hydrocarbon exposure leads to behavioral deficits and downregulation of receptor tyrosine kinase, MET. Toxicological sciences : an official journal of the Society of Toxicology, 118(2):625-634. http://www.citeulike.org/group/6113/article/8357284

Lin, C.-H. H., Chen, C.-C. C., Chou, C.-M. M., Wang, C.-Y. Y., Hung, C.-C. C., Chen, J. Y., Chang, H.-W. W., Chen, Y.-C. C., Yeh, G. C. C., and Lee, Y.-H. H. (2009). Knockdown of the aryl hydrocarbon receptor attenuates excitotoxicity and enhances NMDA-induced BDNF expression in cortical neurons. Journal of neurochemistry, 111(3):777-789. http://www.citeulike.org/user/HEIRS/article/5817355?show_msg=already_posted
Jiang, X., Tian, F., Mearow, K., Okagaki, P., Lipsky, R. H., and Marini, A. M. (2005). The excitoprotective effect of N-methyl-D-aspartate receptors is mediated by a brain-derived neurotrophic factor autocrine loop in cultured hippocampal neurons. Journal of neurochemistry, 94(3):713-722.  http://www.citeulike.org/user/HEIRS/article/258195
Tuon, T., Valvassori, S. S., Lopes-Borges, J., Fries, G. R., Silva, L. A., Kapczinski, F., Quevedo, J., and Pinho, R. A. (2010). Effects of moderate exercise on cigarette smoke exposure-induced hippocampal oxidative stress values and neurological behaviors in mice. Neuroscience letters, 475(1):16-19. http://www.citeulike.org/user/HEIRS/article/6900487