Knockdown of the aryl hydrocarbon receptor attenuates excitotoxicity and enhances NMDA-induced BDNF expression in cortical neurons.

"that AhR opposingly regulates NMDA receptor-mediated excitotoxicity and neurotrophism possibly by differentially regulating the expression of synaptic and extrasynaptic NMDA receptors."

Read more: CiteULike: Knockdown of the aryl hydrocarbon receptor attenuates excitotoxicity and enhances NMDA-induced BDNF expression in cortical neurons.:

BDNF, LRRK and Pink and Environment Play Role in Parkinson's Disease~!

"PD risk is modulated by both genetic factors including BDNF, PINK, and LRRK and environmental exposures."

Read more: CiteULike: Lrrk2 S1647T and BDNF V66M interact with environmental factors to increase risk of Parkinson's disease.:

Cellular mechanism responsible for chronic inflammation, type 2 diabetes uncovered

Cellular mechanism responsible for chronic inflammation, type 2 diabetes uncovered

Reduction of Signalling of GSK-3B May Reduce Some Problems in Non-alcoholic Liver Disease~!

High fat diets may caugment environmental illness by disrupting processes in a variety of pathways such as the Nrf2 and contributes to a variety of patholgies including non-alcoholic liver disease. GSK-3b is a protein that can serve as an "on-off switch" for the antioxidant system. A new study shows that knock-down of this protein may provide cells with more resistance to some of the damaging effects of saturated fats in the diet.

 Ibrahim, S. H. et al. Glycogen synthase kinase-3 (GSK-3) inhibition attenuates hepatocyte lipoapoptosis. Journal of hepatology (2010). URL http://dx.doi.org/10.1016/j.jhep.2010.09.039. http://www.citeulike.org/user/HEIRS/article/8365324

The Role of Glycogen Synthase Kinase 3 in Regulating IFN-beta-Mediated IL-10 Production

IL-10 production by IFN-β-stimulated DC was shown to suppress IFN-γ and IL-17 production by myelin oligodendrocyte glycoprotein-specific CD4(+) T cells, and this IL-10-dependent anti-inflammatory effect was enhanced by directly targeting GSK3 in DC.

Wang, H. et al. The role of glycogen synthase kinase 3 in regulating ifn-beta-mediated il-10 production. Journal of immunology (Baltimore, Md. : 1950) (2010). URL http://dx.doi.org/10.4049/jimmunol.1001473. http://www.citeulike.org/user/HEIRS/article/8443481

Cells' Natural Defence Against Cancer-Causing Viruses Discovered

Cells' Natural Defence Against Cancer-Causing Viruses Discovered

Compound With Potent Effects on the Biological Clock Discovered

Using automated screening techniques developed by pharmaceutical companies to find new drugs, researchers from UC San Diego and three other research institutions have discovered a molecule with the most potent effects ever seen on the biological clock. Dubbed "longdaysin," for its ability to dramatically slow down the biological clock...

Read more: Compound With Potent Effects on the Biological Clock Discovered

Proteins in Bone Health, Development and Disease in Environmental Illness

Proteins in Bone Health, Development and Disease in Environmental Illness

Study: Polymorphisms in Cytokines May Contribute to Autoimmune Disease in Canadian Aboriginal Populations~!

This has implications for conditions where methylation and polymorphisms that effect control of cytokines as well, including the Nrf2 pathway!


Larcombe, L. et al. Differential cytokine genotype frequencies among Canadian Aboriginal and Caucasian populations. Genes and Immunity 6, 140-144 (2004). URL http://dx.doi.org/10.1038/sj.gene.6364157.

New model for the origin of rheumatoid arthritis

New model for the origin of rheumatoid arthritis

Rheumatoid Arthritis & Anti-Citrulline Antibody: Rheumatology Research is Ongoing

Rheumatoid Arthritis & Anti-Citrulline Antibody: Rheumatology Research is Ongoing

Wine Compound Improves Symptom of CFS - Study

Wine Compound Improves Symptom of CFS - Study

Sevoflurane Impairs Olfactory Memory.....

Comment: I expect that this has important implications on animals as well as, humans. Probably more so in animals that use olfactory cues more than humans. If anestethics can cause changes in olfactive memory it would be interesting to consider how other environmental factors may also influence this ability, the extent and how long the effects last.

Kostopanagiotou, G. et al. Sevoflurane impairs post-operative olfactory memory but preserves olfactory function. European journal of anaesthesiology 28, 63-68 (2011). URL http://dx.doi.org/10.1097/EJA.0b013e328340702b.

Flavonoids May Modulate BDNF and Amyloid In Alzheimer's ~!

"stimulating BDNF and reducing Aβ toxicity by natural flavonols provide a therapeutic implication for treatment of AD."


Hou, Y. et al. Anti-depressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice. Neuropharmacology 58, 911-920 (2010). URL http://dx.doi.org/10.1016/j.neuropharm.2009.11.002.


Related:
Health and Environmental Illness Blog: Solvents, PAHs and BDNF as a Modulator of TrkB, Anxiety and Nrf2~!

Nrf2's Regulation of NRF1 and Its Influence on NMDA Subunits and Environmental Illness - see comments.

BDNF and Other Neutrophic Factors May Prevent Seizures and Assoc. Inflammation!

Bovolenta, R. et al. Hippocampal FGF-2 and BDNF overexpression attenuates epileptogenesis-associated neuroinflammation and reduces spontaneous recurrent seizures. Journal of neuroinflammation 7, 81+ (2010). URL http://dx.doi.org/10.1186/1742-2094-7-81.

Mitochondrially encoded methionine is inversely related to longevity in mammals

Mitochondrially encoded methionine is inversely related to longevity in mammals

Downstream mechanisms of nitric oxide-mediated skeletal muscle glucose uptake during contraction.

In oher blogs, I discuss this pathway alot in reference to a number of conditions in environmental illness. In addition, I also mention how specific toxicants may "knock-out" this pathway and therefore provides clues into understanding chemical sensitivity and certain exposures. Unfortunately, it also provides evidence that some therapies that are advocated and out there in the mainstream may be counterproductive depending on the symptoms experienced. Of course, this is up to therapy doctors to determine.

"NOS-derived oxidants regulate skeletal muscle glucose uptake during ex vivo contractions via a cGMP/PKG-, AMPK-, and p38 MAPK-independent pathway. In addition, it appears that NO and ROS may regulate skeletal muscle glucose uptake during contraction through a similar pathway."



Merry, T. L., Lynch, G. S. & McConell, G. K. Downstream mechanisms of nitric oxide-mediated skeletal muscle glucose uptake during contraction. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 299, R1656-R1665 (2010). URL http://dx.doi.org/10.1152/ajpregu.00433.2010.

Hyperthermia-induced Hsp90·eNOS Preserves Mitochondrial Respiration in Hyperglycemic EC by Down-regulating Glut-1 and Up-regulating G6PD Activity

'the present study provides a novel mechanism wherein the reduced oxidative stress in heat-shocked hyperglycemic cells down-regulates Glut-1 and glucose uptake, and fine-tuning of this pathway may be a potential approach to use for therapeutic benefit of diabetes mellitus."

Presley, T., Vedam, K., Druhan, L. J. & Ilangovan, G. Hyperthermia-induced Hsp90·eNOS Preserves Mitochondrial Respiration in Hyperglycemic Endothelial Cells by Down-regulating Glut-1 and Up-regulating G6PD Activity. Journal of Biological Chemistry 285, 38194-38203 (2010). URL http://dx.doi.org/10.1074/jbc.M110.147728.  http://www.citeulike.org/user/HEIRS/article/8399736

HEIRS Library Tags: Hsp90

Master Transcriptional - Definition and Scientific Information - Page 1

Master Transcriptional - Definition and Scientific Information - Page 1

Western Diet May Contribute to Intestinal Motility Problems via Altered Hormone Levels~!

CiteULike: A Western Diet Increases Serotonin Availability in Rat Small Intestine.: "Bertrand, R. L., Senadheera, S., Markus, I., Liu, L., Howitt, L., Chen, H., Murphy, T. V., Sandow, S. L., and Bertrand, P. P. (2010). A Western Diet Increases Serotonin Availability in Rat Small Intestine. Endocrinology."

CiteULike: NEUROTROPHIN/ RECEPTOR EXPRESSION IN URINARY BLADDER OF MICE WITH OVEREXPRESSION OF NGF IN UROTHELIUM.

CiteULike: NEUROTROPHIN/ RECEPTOR EXPRESSION IN URINARY BLADDER OF MICE WITH OVEREXPRESSION OF NGF IN UROTHELIUM.: "Increased voiding frequency in NGF-OE mice was confirmed by examining urination patterns. BDNF, TrkA and TrkB protein expression was significantly (p ≤ 0.01) reduced and p75(NTR) protein expression was significantly (p ≤ 0.01) increased in urinary bladder of NGF-OE mice."

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

Microglia: Giving out dangerous signals - Cell Signaling Update - Signaling Gateway

"The release of heat-shock protein HSP60 from injured neurons activates Toll-like receptor 4 (TLR4) signaling, which stimulates microglia and facilitates neurodegeneration."

Read more: Microglia: Giving out dangerous signals - Cell Signaling Update - Signaling Gateway:

Microglia: Giving out dangerous signals - Cell Signaling Update - Signaling Gateway

"The release of heat-shock protein HSP60 from injured neurons activates Toll-like receptor 4 (TLR4) signaling, which stimulates microglia and facilitates neurodegeneration."

Read more: Microglia: Giving out dangerous signals - Cell Signaling Update - Signaling Gateway:

Assessment of 3-nitropropionic acid-evoked peripheral neuropathy in rats: neuroprotective effects of acetyl-l-carnitine and resveratrol.

"resveratrol is a good candidate for treatment of metabolic neuropathy. The experimental outcome of this study shows that chronic treatment with 3-NPA in rats is relevant in development of an experimental model of toxic neuropathy."

Read more: CiteULike: Assessment of 3-nitropropionic acid-evoked peripheral neuropathy in rats: neuroprotective effects of acetyl-l-carnitine and resveratrol.:

Elevated Levels of Ammonia Impair the NO/cGMP Through Alterations of Cellular Transporters~!

In other blogs, I have suggested that alterations in the NO/cGMP pathway by environmental factors may influence environmental disease including CFS and MCS. Several recent studies have suggested a relationship between the NO/cGMP pathway and the activation of the Nrf2. Because the Nrf2 has a neuroprotective role on astrocytes and neurons, the failure of this pathway could contribute to neurological damage commonly associated with aging as well as, other neurological disorders. In this most recent study, the author provides more evidence that in cases of hyperammonemia, the No/cGMP pathway activity is decreased and therefore, may provide some explanation for damage resulting from high ammonia levels.

"reduced delivery of Arg due to enhanced y(+)LAT2-mediated exchange of extracellular Gln for intracellular Arg may contribute to the decrease of NO/cGMP pathway activity evoked in the brain by HA."

Zielińska, M., Ruszkiewicz, J., Hilgier, W., Fręśko, I., and Albrecht, J. (2010). Hyperammonemia increases the expression and activity of the glutamine/arginine transporter y(+)LAT2 in rat cerebral cortex: implications for the nitric oxide/cGMP pathway. Neurochemistry international. http://www.citeulike.org/user/HEIRS/article/8341074
Sidoryk-Wegrzynowicz, M., Wegrzynowicz, M., Lee, E., Bowman, A., and Aschner, M. (2010). Role of Astrocytes in Brain Function and Disease. Toxicologic pathology.  http://www.citeulike.org/user/HEIRS/article/8341171