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Nathan Goodyear

Methylmercury induces oxidative injury, alterations in permeability and glutamine trans... - 0 views

www.ncbi.nlm.nih.gov/...PMC1847599

methylmercury mercury astrocytes glutamate mitochondria brain inflammation oxidative ROS

shared by Nathan Goodyear on 26 Nov 13 - No Cached
  • Nathan Goodyear on 26 Nov 13
     
    methylmercury mediates neurotoxicity via mitochondrial damage, inflammation, and oxidative stress.  Astrocytes accumulated the methyl mercury.  The destruction of the astrocytes will result in an increase in glutamate.  Methylmercury is synergistic with other toxins in the development of immunoexcitotoxicity.
Nathan Goodyear

Lipopolysaccharide (LPS) potentiates hydrogen peroxide toxicity in T98G astrocytoma cel... - 0 views

www.ncbi.nlm.nih.gov/...PMC2631585

LPS lipopolysaccharides microglia astrocytes brain H2O2 inflammation

shared by Nathan Goodyear on 21 Sep 17 - No Cached
  • Nathan Goodyear on 21 Sep 17
     
    good review of proposed mechanism of how LPS aids in cell death of astrocytes in vivo: LPS damages the endothelium of the BBB, leading to increase permeability.  This exposes astrocytes to LPS directly.  LPS suppressed genetic expression of antioxidant genes.  LPS stimulates cytokine production, including the production of H2O2 from microglial cells in the brain.  An up regulation of iNOS occurs and in the presence of weakened ability to protect against NO and its metabolites occurs.  
Nathan Goodyear

Access : Neuroimmunology: Estrogen receptor ligands suppress inflammatory responses in ... - 0 views

www.nature.com/...nrneurol.2011.87.html

ER-beta estrogen receptors receptor MS multiple sclerosis astrocytes microglia microglial cells excitotoxic excitotoxicity disease neurology brain immune hormone hormones

shared by Nathan Goodyear on 10 Oct 12 - No Cached
  • Nathan Goodyear on 10 Oct 12
     
    Granted, this study was in an animal model of MS, but signaling through ER-beta was shown to decrease inflammation from astrocytes and microglial cells in the brain.  These immune cells are known to play prominent roles in excitotoxic diseases such as MS.  So, again, it is not just about the message, but also about how the message is interpreted.
Nathan Goodyear

Astrocytes and therapeutics for Parkinson'... [Neurotherapeutics. 2010] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...20880505

Astrocytes neurodegenerative disorders disease Parkinson's ALS

shared by Nathan Goodyear on 14 Dec 11 - No Cached
  • Nathan Goodyear on 14 Dec 11
     
    astrocytes play role in neurodegenerative disorders.
Nathan Goodyear

Membrane Estrogen Receptors Stimulate Intracellular Calcium Release and Progesterone Sy... - 0 views

www.jneurosci.org/...12950.full

estradiol estrogen progesterone hypothalamus receptors ER ER-alpha ER alpha hormones CNS astrocytes brain calcium channels

shared by Nathan Goodyear on 10 Mar 14 - No Cached
  • Nathan Goodyear on 10 Mar 14
     
    Estradiol stimulates hypothalamic progesterone synthesis in astrocytes in rat model.  This occurs through activation of calcium channels and influx of calcium.  ER alpha appears to be the prominent ER involved.
Nathan Goodyear

Changes in the number of astrocytes and micr... [Neurotoxicology. 1996] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...8784824

methylmercury brain inorganic mercury astrocyte microglia

shared by Nathan Goodyear on 26 Nov 13 - No Cached
  • Nathan Goodyear on 26 Nov 13
     
    low methylmercury shown to accumulate in the brains of monkeys in the form of inorganic mercury.  Specifically, astrocytes and microglial cells accumulated the inorganic mercury.  Long-term low exposure can result in neuro-accumulation of inorganic mercury and neurotoxicity.
Nathan Goodyear

Thyroid hormone treated astrocytes induce maturation of cerebral cortical neurons throu... - 0 views

www.ncbi.nlm.nih.gov/...PMC3740295

thyroid hormone T3 astrocyte brain health cognition disease

shared by Nathan Goodyear on 24 Sep 14 - No Cached
  • Nathan Goodyear on 24 Sep 14
     
    T3 plays a significant role in astrocyte maturation.  This has significant cognitive and disease impact.
Nathan Goodyear

Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxid... - 0 views

www.ncbi.nlm.nih.gov/...PMC3180189

cancer reverse warburg effect warburg effect NF-kapppB HIF-1alpha Cav-1 H2O2

shared by Nathan Goodyear on 12 Nov 14 - No Cached
  • reducing oxidative stress with powerful antioxidants, is an important strategy for cancer prevention, as it would suppress one of the key early initiating steps where DNA damage and tumor-stroma metabolic-coupling begins. This would prevent cancer cells from acting as metabolic “parasites
  • Oxidative stress in cancer-associated fibroblasts triggers autophagy and mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the “reverse Warburg effect.
  • Then, oxidative stress, in cancer-associated fibroblasts, triggers the activation of two main transcription factors, NFκB and HIF-1α, leading to the onset of inflammation, autophagy, mitophagy and aerobic glycolysis in the tumor microenvironment
  • ...38 more annotations...
  • oxidative stress and ROS, produced in cancer-associated fibroblasts, has a “bystander effect” on adjacent cancer cells, leading to DNA damage, genomic instability and aneuploidy, which appears to be driving tumor-stroma co-evolution
  • tumor cells produce and secrete hydrogen peroxide, thereby “fertilizing” the tumor microenvironment and driving the “reverse Warburg effect.”
  • This type of stromal metabolism then produces high-energy nutrients (lactate, ketones and glutamine), as well as recycled chemical building blocks (nucleotides, amino acids, fatty acids), to literally “feed” cancer cells
  • loss of stromal caveolin (Cav-1) is sufficient to drive mitochondrial dysfunction with increased glucose uptake in fibroblasts, mimicking the glycolytic phenotype of cancer-associated fibroblasts.
  • oxidative stress initiated in tumor cells is transferred to cancer-associated fibroblasts.
  • Then, cancer-associated fibroblasts show quantitative reductions in mitochondrial activity and compensatory increases in glucose uptake, as well as high ROS production
  • These findings may explain the prognostic value of a loss of stromal Cav-1 as a marker of a “lethal” tumor microenvironment
  • aerobic glycolysis takes place in cancer-associated fibroblasts, rather than in tumor cells, as previously suspected.
  • our results may also explain the “field effect” in cancer biology,5 as hydrogen peroxide secreted by cancer cells, and the propagation of ROS production, from cancer cells to fibroblasts, would create an increasing “mutagenic field” of ROS production, due to the resulting DNA damage
  • Interruption of this process, by addition of catalase (an enzyme that detoxifies hydrogen peroxide) to the tissue culture media, blocks ROS activity in cancer cells and leads to apoptotic cell death in cancer cells
  • In this new paradigm, cancer cells induce oxidative stress in neighboring cancer-associated fibroblasts
  • cancer-associated fibroblasts have the largest increases in glucose uptake
  • cancer cells secrete hydrogen peroxide, which induces ROS production in cancer-associated fibroblasts
  • Then, oxidative stress in cancer-associated fibroblast leads to decreases in functional mitochondrial activity, and a corresponding increase in glucose uptake, to fuel aerobic glycolysis
  • cancer cells show significant increases in mitochondrial activity, and decreases in glucose uptake
  • fibroblasts and cancer cells in co-culture become metabolically coupled, resulting in the development of a “symbiotic” or “parasitic” relationship.
  • cancer-associated fibroblasts undergo aerobic glycolysis (producing lactate), while cancer cells use oxidative mitochondrial metabolism.
  • We have previously shown that oxidative stress in cancer-associated fibroblasts drives a loss of stromal Cav-1, due to its destruction via autophagy/lysosomal degradation
  • a loss of stromal Cav-1 is sufficient to induce further oxidative stress, DNA damage and autophagy, essentially mimicking pseudo-hypoxia and driving mitochondrial dysfunction
  • loss of stromal Cav-1 is a powerful biomarker for identifying breast cancer patients with early tumor recurrence, lymph-node metastasis, drug-resistance and poor clinical outcome
  • this type of metabolism (aerobic glycolysis and autophagy in the tumor stroma) is characteristic of a lethal tumor micro-environment, as it fuels anabolic growth in cancer cells, via the production of high-energy nutrients (such as lactate, ketones and glutamine) and other chemical building blocks
  • the upstream tumor-initiating event appears to be the secretion of hydrogen peroxide
  • one such enzymatically-active protein anti-oxidant that may be of therapeutic use is catalase, as it detoxifies hydrogen peroxide to water
  • numerous studies show that “catalase therapy” in pre-clinical animal models is indeed sufficient to almost completely block tumor recurrence and metastasis
  • by eliminating oxidative stress in cancer cells and the tumor microenvironment,55 we may be able to effectively cut off the tumor's fuel supply, by blocking stromal autophagy and aerobic glycolysis
  • breast cancer patients show systemic evidence of increased oxidative stress and a decreased anti-oxidant defense, which increases with aging and tumor progression.68–70 Chemotherapy and radiation therapy then promote further oxidative stress.69 Unfortunately, “sub-lethal” doses of oxidative stress during cancer therapy may contribute to tumor recurrence and metastasis, via the activation of myofibroblasts.
  • a loss of stromal Cav-1 is associated with the increased expression of gene profiles associated with normal aging, oxidative stress, DNA damage, HIF1/hypoxia, NFκB/inflammation, glycolysis and mitochondrial dysfunction
  • cancer-associated fibroblasts show the largest increases in glucose uptake, while cancer cells show corresponding decreases in glucose uptake, under identical co-culture conditions
  • Thus, increased PET glucose avidity may actually be a surrogate marker for a loss of stromal Cav-1 in human tumors, allowing the rapid detection of a lethal tumor microenvironment.
  • it appears that astrocytes are actually the cell type responsible for the glucose avidity.
  • In the brain, astrocytes are glycolytic and undergo aerobic glycolysis. Thus, astrocytes take up and metabolically process glucose to lactate.7
  • Then, lactate is secreted via a mono-carboxylate transporter, namely MCT4. As a consequence, neurons use lactate as their preferred energy substrate
  • both astrocytes and cancer-associated fibroblasts express MCT4 (which extrudes lactate) and MCT4 is upregulated by oxidative stress in stromal fibroblasts.34
  • In accordance with the idea that cancer-associated fibroblasts take up the bulk of glucose, PET glucose avidity is also now routinely used to measure the extent of fibrosis in a number of human diseases, including interstitial pulmonary fibrosis, postsurgical scars, keloids, arthritis and a variety of collagen-vascular diseases.
  • PET glucose avidity and elevated serum inflammatory markers both correlate with poor prognosis in breast cancers.
  • PET signal over-estimates the actual anatomical size of the tumor, consistent with the idea that PET glucose avidity is really measuring fibrosis and inflammation in the tumor microenvironment.
  • human breast and lung cancer patients can be positively identified by examining their exhaled breath for the presence of hydrogen peroxide.
  • tumor cell production of hydrogen peroxide drives NFκB-activation in adjacent normal cells in culture6 and during metastasis,103 directly implicating the use of antioxidants, NFκB-inhibitors and anti-inflammatory agents, in the treatment of aggressive human cancers.
  • Nathan Goodyear on 12 Nov 14
     
    Good description of the communication between cancer cells and fibroblasts.  This theory is termed the "reverse Warburg effect".
Nathan Goodyear

Transrepression of Inflammation -- Foley 4 (173): ec141 -- Science Signaling - 0 views

stke.sciencemag.org/...ec141

ER-beta inflammation microglia astrocyte MS multiple sclerosis autoimmune disease

shared by Nathan Goodyear on 06 Oct 12 - No Cached
  • Nathan Goodyear on 06 Oct 12
     
    ER-beta agonist activity/agnoists inhibit inflammatory gene expression in microglia and astrocyte cells.
Nathan Goodyear

Aluminum-induced Defective Mitochondrial Metabolism Perturbs Cytoskeletal Dynamics in H... - 0 views

www.academia.edu/...ics_in_Human_Astrocytoma_Cells

aluminum astrocytes brain inflammation neurology AL

shared by Nathan Goodyear on 25 Nov 13 - No Cached
  • Nathan Goodyear on 25 Nov 13
     
    Aluminum destructive to astrocytes in the brain.
Nathan Goodyear

Progesterone induces the growth and infiltrat... [Biomed Res Int. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24982875

Progesterone cancer astrocytes brain hormone hormones metabolites

shared by Nathan Goodyear on 07 Jul 14 - No Cached
  • Nathan Goodyear on 07 Jul 14
     
    Progesterone shown to stimulate growth and migration of astrocytes in the brain.  The has both implications in cancer, such as in astrocytomas, but also in TBI.  The study also found that the Progesterone antagonist RU486 inhibited this effect.  A more thorough evaluation would have included the pregnane metabolites.
Nathan Goodyear

Age Increase of Estrogen Receptor-α (ERα) in Cortical Astrocytes Impairs Neur... - 0 views

endo.endojournals.org/...2101.abstract

ER alpha ER-alpha ER estrogen receptors brain neurology neurotrophic astrocytes

shared by Nathan Goodyear on 24 Jun 13 - No Cached
  • Nathan Goodyear on 24 Jun 13
     
    increased ER-alpha expression associated with decreased neurotrophic activity.  A decrease in the neurotrophic activity of the aging brain is associated with many of the diseases of the aging brain. The major point here is that ER-alph is known to increase inflammatory signaling.  So increased inflammation, just via the ER receptors, plays a role in the aging brain.
Nathan Goodyear

Diabetic neuropathic pain: a role for testosterone metabolites - 0 views

joe.endocrinology-journals.org/...1.abstract

diabetes neuropathy pain diabetic DHT androgens 3 alpha-androstanediol metabolites Testosterone androgen male hormone hormones

shared by Nathan Goodyear on 24 Mar 14 - No Cached
  • Nathan Goodyear on 24 Mar 14
     
    Great article.  Really shows the depth of the androgens and androgen metabolites in diabetes and diabetic complications.  In this study, DHT and its metabolis 3-alpha androstanediol were shown to reduce inflammation and pain associated with diabetic neuropathy.  Significant reduction in inflammation signaling (IL-1beta, TNF-alpha) was seen as was potential neurodegenerative processes (glutamate release and astrocyte immunoreactivity).
Nathan Goodyear

Minimal Penetration of Lipopolysaccharide Across the Murine Blood-brain Barrier - 0 views

www.ncbi.nlm.nih.gov/...PMC2789209

LPS lipopolysaccharides brain blood brain barrier

shared by Nathan Goodyear on 21 Sep 17 - No Cached
  • Nathan Goodyear on 21 Sep 17
     
    Study finds very small % of LPS actually is able to penetrate BBB, yet based on other studies, this is enough to trigger microglial activation and damage/death to astrocytes and other brain cells.
Nathan Goodyear

Kynurenine Metabolites and Migraine: Experimental Studies and Therapeutic Perspectives - 0 views

www.ncbi.nlm.nih.gov/...PMC3131728

migraine headaches headache NMDA tryptophan Kynurenine pathway quinolinate glial cells astrocytes

shared by Nathan Goodyear on 26 Sep 13 - No Cached
  • Nathan Goodyear on 26 Sep 13
     
    Disordered tryptophan metabolism and migraine headaches.
Nathan Goodyear

Aluminum induced immunoexcitotoxicity in neurodevelopmental and neurodegenerative disor... - 0 views

www.geoengineeringwatch.org/...Aluminum-Blaylock.pdf

Aluminum immunoexcitotoxicity neurodegenerative disease disorders glial microglia astrocytes glutathione Alzheimer's Parkinson's MS

shared by Nathan Goodyear on 26 Nov 13 - No Cached
  • Nathan Goodyear on 26 Nov 13
     
    Great review of the scientific evidence of Aluminum in microglial activation and immunoexcitotoxicity and neurodegeneration of the brain.
Nathan Goodyear

Untitled Page - 0 views

www.cnsspectrums.com/...article_pf.aspx

inflammation glutamic acid glutamate glia astrocytes depression disordered tryptophan metabolism

shared by Nathan Goodyear on 14 Sep 11 - No Cached
  • Nathan Goodyear on 14 Sep 11
     
    review of inflammation, glutamic acid, glial activation and depression
Nathan Goodyear

Dynamic Changes in Dopaminergic Neurotransmission Induced by a Low Concentration of Bis... - 0 views

onlinelibrary.wiley.com/...full

BPA Bisphenol-A dopamine mesolimbic system psychological dependence

shared by Nathan Goodyear on 10 Oct 11 - No Cached
  • Nathan Goodyear on 10 Oct 11
     
    BPA and changes in the mesolimbic/dopamine system
Nathan Goodyear

1210_article_14 - 0 views

jpp.krakow.pl/...14_article.html

neurotoxic thimerosal vaccinations

shared by Nathan Goodyear on 03 Apr 11 - No Cached
  • These modulatory effects - which most likely involve binding with functional thiol residues - are interwoven with neurotoxic actions of both mercurials.
  • THIM is metabolized in the body to ethyl mercury (EtHg) and subsequently to inorganic mercury forms, which accumulate in tissues of vital organs, including the brain (22). Information about neurochemical and neurotoxic effects of THIM is still limited, but the existing data indicate that in pharmacodynamics and toxicity THIM/EtHg does not differ significantly from methyl mercury (MeHg), which has been studied more extensively, although these compounds differ somewhat in pharmacokinetics (8).
  • Several studies documented that the neurotoxic effects of mercurials involve glutamate-mediated excitotoxicty, due to their ability to inhibit uptake of glutamate in astrocytes, resulting in an increase of the extracellular level of this excitatory amino acid
  • Nathan Goodyear on 03 Apr 11
     
    neurotoxic effects of thimerosal
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