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

Brain's Link Between Sounds, Smells and Memory Revealed | Anxiety Disorders | LiveScience

"Sights, sounds and smells can all evoke emotionally charged memories. A new study in rats suggests why: The same part of the brain that's in charge of processing our senses is also responsible, at least in part, for storing emotional memories."

Read more: Brain's Link Between Sounds, Smells and Memory Revealed Anxiety Disorders LiveScience:

HO/CO and NO Regulate Oxytocin - Anxiety and Autism Implications?

Considering the relationship of oxytocin to behaviors such as fear, aggression and attachment, this study may have significant implications for PTSD as well as social problems such as violence and neglect. Also, it presents a question of whether a decline in the antioxidant system may also positively or negatively have an influence because it regulates HO-1.

Blockade of HO inhibited both basal and osmotically stimulated OT release, and induced a marked increase in NOS activity. These results indicate the involvement of CO in the regulation of NOS activity. The present data demonstrate that hypothalamic OT release induced by osmotic stimuli is modulated, at least in part, by interactions between NO and CO.

CiteULike: Carbon monoxide and nitric oxide modulate hyperosmolality-induced oxytocin secretion by the hypothalamus in vitro.: "Gomes, D. A. A., Giusti-Paiva, A., Ventura, R. R. R., Elias, L. L. K. L., Cunha, F. Q. Q., and Antunes-Rodrigues, J. (2010). Carbon monoxide and nitric oxide modulate hyperosmolality-induced oxytocin secretion by the hypothalamus in vitro. Bioscience reports, 30(5):351-357."

Boosting Brain Hormone May Have PTSD/Anxiety Implications

Boosting BDNF activity in hippocampal-infralimbic circuits may ameliorate disorders of learned fear.

CiteULike: Induction of fear extinction with hippocampal-infralimbic BDNF.: "Peters, J., Dieppa-Perea, L. M., Melendez, L. M., and Quirk, G. J. (2010). Induction of fear extinction with hippocampal-infralimbic bdnf. Science (New York, N.Y.), 328(5983):1288-1290."

Exercise Is Good Medicine For Preventing And Reducing An Angry Mood

Exercise Is Good Medicine For Preventing And Reducing An Angry Mood

Gulf War and Health: Links to Fibromalgia, PTSD, IBS

IOM determines that Gulf War service causes post-traumatic stress disorder (PTSD) and that service is associated with multisymptom illness; gastrointestinal disorders such as irritable bowel syndrome; alcohol and other substance abuse; and anxiety disorders and other psychiatric disorders. To ensure that our veterans receive the best possible care, now and in the future, the government should continue to monitor their health and conduct research to identify the best treatments to assist Gulf War veterans still suffering from persistent, unexplained illnesses. The report also says there is some limited evidence of a link to fibromyalgia and ALS but the connection is less clear. Read more.

Il-6 Modulates CRF in the Hypothalamus in Response to Different Signals.

Module: 5/22/2010

Background: CRF can regulate signaling in response to different odors. In those cases, it can lead to an anxiolytic or elevation and other responses typical of the stress response including pain generation, immune regulation, itch, rash and other changes such as gastric function alterations. Of course, these are symptoms characteristic of chemical sensitivity and also some symptoms characteristic of other environmentally influenced conditions such as CFS and sickness syndrome.

A major regulator of sickness syndrome is Il-6 which can be functionally modulated through Il-10 and ultimately most probably HO-1 which has been shown in other studies to increase during exercise. Interestingly, one can identify similarities in cancer-related fatigue to some chronic symptoms of CFS and sickness syndrome including the exhausting fatigue and cachexia that is exhibited in the latter, in animals and humans. Preliminary studies suggest cytokine Il-6/Il-8 may modulate the severity of cancer-related fatigue and others show cancer-related fatigue is common with serotonin dysregulation. Coincidentally, in the trout corticotrophin activation by ammonia is associated with alterations in neurotransmitter levels including dopamine and serotonin. So here again, we see potential especially with periods of aberrant corticotrophin signalling, where symptoms of environmental illness such as anxiety, depression, weakeness and fatigue may present itself. These findings supports past studies that suggest that fatigue in CFS may be in part due to serotonin dysregulation and elevations in Il-6.(Ryan)

CiteULike: Transcriptional regulation of hypothalamic corticotropin-releasing factor gene.: "Glucocorticoid-dependent repression of cAMP-stimulated CRF promoter activity is mediated by both nGRE and SRE in hypothalamic cells. Interleukin (IL)-6 produced in the hypothalamus stimulates the CRF gene. Suppressor of cytokine signaling-3, which is induced by a cAMP stimulant and IL-6, is involved in the negative regulation of CRF gene expression in hypothalamic cells. Such complex mechanisms would contribute to stress responses and homeostasis in the hypothalamus."

Related: Hummel, M., Cummons, T., Lu, P., Mark, L., Harrison, J. E., Kennedy, J. D., and Whiteside, G. T. (2010). Pain is a salient ßtressor" that is mediated by corticotropin- releasing factor-1 receptors. Neuropharmacology.
http://www.citeulike.org/user/HEIRS/article/7177466
Coric, V., Feldman, H. H., Oren, D. A., Shekhar, A., Pultz, J., Dockens, R. C., Wu, X., Gentile, K. A., Huang, S.-P. P., Emison, E., Delmonte, T., D'Souza, B. B., Zimbroff, D. L., Grebb, J. A., Goddard, A. W., and Stock, E. G. (2010). Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder. Depression and anxiety, 27(5):417-425.
http://www.citeulike.org/user/HEIRS/article/7193107
Theoharides, T. C., Singh, Boucher, W., Pang, X., Letourneau, R., Webster, E., and Chrousos, G. (1998). Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects. Endocrinology, 139(1):403-413.
http://www.citeulike.org/user/HEIRS/article/7207688
Mustian, K. M., Fisher, S., Adams, J., Janelsins, M., Palesh, O., Darling, T., Peppone, L., Heckler, C., Williams, J., and Morrow, G. (2009). Cytokine-mediated changes associated with improvements in cancer-related fatigue induced by exercise: Results from a randomized pilot study of cancer patients receiving radiotherapy. Journal of Clinical Oncology, 27(15s).
http://www.citeulike.org/user/HEIRS/article/7207720
Ryan, J. L., Carroll, J. K., Ryan, E. P., Mustian, K. M., Fiscell, K., and Morrow, G. R. (2007). Mechanisms of cancer-related fatigue. The Oncologist, 12(1 supp):22-34.
http://www.citeulike.org/user/HEIRS/article/7207823

Cognitive-affective characteristics of smokers with and without posttraumatic stress disorder and panic psychopathology.

New study shows differences in anxiety from exposure to cigarette smoke.
Implications for differentiation of panic attacks, panic disorder and post
traumatic syndrome.

CiteULike: Cognitive-affective characteristics of smokers with and without posttraumatic stress disorder and panic psychopathology.: "Vujanovic, A. A., Marshall, E. C., Gibson, L. E., and Zvolensky, M. J. (2010). Cognitive-affective characteristics of smokers with and without posttraumatic stress disorder and panic psychopathology. Addictive behaviors, 35(5):419-425."

Melatonin Metabolite Levels Associated with Migraine

Title: Urinary 6-sulphatoxymelatonin levels are depressed in chronic migraine and several comorbidities

Summary: This study suggest a relationship between urinary melatonin and migraine. An inverse correlation of melatonin to anxiety, depression and fatigue that points to a hypothalamic function in migraine.

Citation: Masruha, M. R., Lin, J., de Souza Vieira, D. S., Minett, T. S., Cipolla-Neto, J., Zukerman, E., Vilanova, L. C., and Peres, M. F. (2009). Urinary 6-sulphatoxymelatonin levels are depressed in chronic migraine and several comorbidities. Headache. http://www.citeulike.org/user/HEIRS/article/5947791