TNF-Alpha
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Dr. George Church discusses revolutionary technologies in the field of genetic engineering.
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Dr. George Church discusses revolutionary technologies in the field of genetic engineering.
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Blocking soluble TNF signaling attenuates loss of dopaminergic neurons in models of Parkinson’s disease. (2006) www.sciencedaily.com
Blocking the action of TNF-alpha may slow the progression of Parkinson’s disease.
Parkinson’s disease is a progressive neurodegenerative disorder that affects the central nervous system. It is caused by the destruction of nerve cells in the part of the brain called the substantia nigra. Approximately 1 percent of all adults over the age of 60 years lives with Parkinson’s disease. Findings from a 2006 study suggest that blocking the action of tumor necrosis factor-alpha slows the progression of Parkinson’s disease.
Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that is produced by a wide range of cells, including macrophages, lymphocytes, glial cells, and others. TNF-alpha signaling inhibits tumorigenesis, prevents viral replication, and induces fever and apoptosis. Dysregulation of the TNF-alpha signaling pathway has been implicated in a variety of disorders, including cancer, autoimmune diseases, Alzheimer’s disease, and depression.
The investigators injected the brains of mice with either lipopolysaccharide (LPS, an endotoxin that promotes acute inflammation) or 6-hydroxydopamine (a neurotoxin) and assessed the animals' brains for evidence of substantia nigra cell death. They injected a compound called XENP345 (a TNF-alpha inhibitor) into the brains of some of the mice. They also applied LPS and 6-hydroxydopamine to cultured neuronal cells and assessed the effects of XENP345 on cell death.
They found that both LPS and 6-hydroxydopamine caused marked cell death in the substantia nigra region of the animals' brains. They also found that inhibiting TNF-alpha via XENP345 in the brains and in cultured cells reduced cell death by roughly half.
These findings suggest that inhibiting the activity of the pro-inflammatory cytokine TNF-alpha reduces cell death in an animal model of Parkinson’s disease. Robust evidence indicates that exercise, which also reduces inflammation, slows the progression of Parkinson’s disease. Learn more about the effects of exercise on Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.
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Probiotics may improve inflammation-associated behavioral changes in mice by lowering TNF-alpha blood levels. (2015) www.sciencedaily.com
Probiotics attenuate inflammation-associated sickness behaviors.
The gut-brain axis, a bidirectional signaling pathway between the gastrointestinal tract and the nervous system, plays critical roles in human health. Key elements of this pathway are the tens of trillions of microbes that comprise the intestinal microbiota. Findings from a 2015 study suggest that probiotics attenuate inflammation-associated sickness behaviors.
Probiotics are typically defined as live microorganisms that, when consumed in sufficient amounts, confer a health benefit on the consumer. They contain a variety of microorganisms, but Lactobacillus and Bifidobacterium bacteria are among the most common. Probiotics can be found in yogurt, kefir, kimchi, and other fermented foods and are widely available as dietary supplements.
Sickness behaviors are adaptive behavioral changes that occur during infection or chronic inflammatory disorders and may include lethargy, depressed mood, appetite loss, sleepiness, pain, or confusion. Evidence suggests that tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine produced by immune cells, activates microglia (the brain’s resident immune cells) and recruits white blood cells to the brain, driving the development of inflammation-associated sickness behaviors.
The investigators used a model of liver inflammation in mice to study the effects of a probiotic on inflammation-associated sickness behavior. Mice with this form of liver inflammation typically have high levels of pro-inflammatory cytokines and exhibit distinct sickness behaviors. They fed the mice either a probiotic or a placebo and then they studied the animals' behavior. They also measured TNF-alpha levels in the animals' blood and the number of activated immune cells in the animals' brains.
They found that although the probiotic did not reduce the severity of liver inflammation in the mice, it did reduce sickness behaviors better than the placebo. Mice that received the probiotics also had lower TNF-alpha levels and fewer activated immune cells in their brains compared to mice that received a placebo.
These findings suggest that probiotics attenuate inflammation-associated sickness behaviors in mice, likely via modulation of the gut-brain axis. Learn about factors to consider when choosing a probiotic supplement in this clip featuring Dr. Jed Fahey.
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TNF-alpha production within the brain may partially explain the behavioral changes in mice with cholestatic liver damage. (2006) www.sciencedaily.com
TNF-alpha in the brain drives sickness behaviors associated with liver disease.
Many liver disorders cause behavioral symptoms, often referred to as sickness behaviors, such as fatigue, loss of appetite, and “brain fog.” Evidence suggests that these symptoms arise from alterations in the central nervous system, but scientists don’t fully understand what drives them. Findings from a 2006 study suggest that sickness behaviors in the setting of cholestasis, a common liver disorder, are caused by the presence of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, in the brain.
Cholestasis is characterized by impaired bile flow and subsequent retention of bile acids, bilirubin, and other substances, including lipopolysaccharide, an endotoxin, in the liver and blood. It is a common disorder of pregnancy but can affect all demographics, including children. Most people with cholestasis report experiencing sickness behaviors, especially fatigue, which occurs in roughly 86 percent of people with the disorder.
TNF-alpha is produced by many types of immune cells. It exists in soluble and transmembrane forms, both of which mediate a variety of opposing physiological and pathological functions, depending on which of its receptors it binds to. For example, binding to TNF receptor 1 promotes apoptosis (programmed cell death) and inflammation; binding to TNF receptor 2 promotes cell survival, resolution of inflammation, immunity, and cellular repair. Elevated TNF-alpha is associated with chronic pain syndromes and anxious behaviors.
The investigators tied off the bile ducts of healthy mice to induce cholestasis. Then they isolated endothelial cells from the blood vessels in the animals' brains to see if the cells were activated and if the cells interacted with immune cells. They also measured TNF-alpha production by monocytes (white blood cells).
They found that endothelial cells were activated in the setting of cholestasis, and these activated cells readily interacted with immune cells that had been recruited to the brain. In turn, the immune cells increased their production of TNF-alpha. In light of the known effects of TNF-alpha on sickness behaviors, these findings suggest that TNF-alpha production in the brain mediates sickness behaviors in mice with liver disease.