TET2 Regulates the Neuroinflammatory Response in Microglia

TET2 upregulation has been shown to improve neurogenesis and cognitive function in old mice. So it is interesting that researchers here link increased expression of TET2 with the inflammatory response of microglia in the brain. The broader context is that is becoming increasingly clear that dysfunctional and inflammatory microglia contribute significantly to the progression of neurodegenerative conditions. This is one of many examples of apparently contradictory results to illustrate the point that cellular biochemistry is very complex. Contradictions usually indicate that there is much left to be understood about the way in which the systems studied fit together in practice. Microglia, the resident immune cells in the central nervous system, are key players in maintaining homeostasis in the brain. Microglia play a wide variety of roles under physiological and pathological conditions. In the healthy brain, microglia are responsible for neuronal activity-dependent synapse pruning during postnatal development. Upon neuronal injury or infection, microglia become rapid responders that initiate an innate inflammatory response. If the inflammatory response is exaggerated or chronic, it becomes detrimental for the surrounding neuronal population, as in Parkinson's disease and Alzheimer's disease. Epigenomic mechanisms regulate distinct aspects of the inflammatory response in immune cells. Despite the central role for microglia in neuroinflammation and neurodegenerat...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs

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In this study, it was found that acetaldehyde treatment induced excessive mitochondrial fragmentation, impaired mitochondrial function and caused cytotoxicity in cortical neurons and SH-SY5Y cells. Further analyses showed that acetaldehyde induced the phosphorylation of mitochondrial fission related protein dynamin-related protein 1 (Drp1) at Ser616 and promoted its translocation to mitochondria. The elevation of Drp1 phosphorylation was partly dependent on the reactive oxygen species (ROS)-mediated activation of c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), as N-acetyl-l-cysteine (NAC) pre...
Source: Redox Biology - Category: Biology Source Type: research
In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT), VKDHet mice, which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and contro...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, the enhanced mice live somewhat longer than their unmodified peers, though not as much longer as is the case for the application of telomerase gene therapy. The mice do also exhibit reduced cancer risk, however. The scientists here class telomere shortening as a cause of aging, which is not a point universally agreed upon. Reductions in average telomere length in tissues looks much more like a downstream consequence of reduced stem cell activity than an independent mechanism. Researchers obtain the first mice born with hyper-long telomeres and show that it is possible to extend life without any geneti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study elucidates the potential to use mitochondria from different donors (PAMM) to treat UVR stress and possibly other types of damage or metabolic malfunctions in cells, resulting in not only in-vitro but also ex-vivo applications. Gene Therapy in Mice Alters the Balance of Macrophage Phenotypes to Slow Atherosclerosis Progression https://www.fightaging.org/archives/2019/07/gene-therapy-in-mice-alters-the-balance-of-macrophage-phenotypes-to-slow-atherosclerosis-progression/ Atherosclerosis causes a sizable fraction of all deaths in our species. It is the generation of fatty deposits in blood vessel...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Mitochondria are crucial for neuronal cell survival and death through their functions in ATP production and the intrinsic pathway of apoptosis. Mitochondrial dysfunction is considered to play a central role in several serious human diseases, including neurodegenerative diseases, such as Parkinson's and Alzheimer's disease and ischemic neurodegeneration. The aim of the present study was to investigate the impact of transient global brain ischemia on the expression of selected proteins involved in mitochondrial dynamics and mitochondria‑associated membranes. The main foci of interest were the proteins mit...
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research
Conclusion Taken together, evidence from animal and human studies demonstrates that the brain detects levels of circulating nutrients and hormones and consequently organizes an outward response that contributes to the regulation of whole-body glucose homeostasis. However, there are major knowledge gaps about the exact nature of this response and its relative importance compared to peripheral processes. As we have seen, animal studies have provided an anatomical map of CNS glucose regulation and have identified important neurons and neural circuits involved. Additionally, the CNS sensing of key nutrients and hormones has b...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
This study was carried out in accordance with the recommendations of “NIH Guide for Care and Use of Laboratory Animal protocols” and of the Institutional Animal Care and Use Committee of Shiga University of Medical Science (SUMS). The protocol was approved by SUMS. Six adult male Balb/c mice (5-weeks-old) were purchased from Clea Japan Inc. (Konan, Japan). Each mouse (labeled H1-H6) received subcutaneous injections of 0.1 ml of TiterMax Gold adjuvant (Sigma-Aldrich, Saint-Louis, MO, USA) containing 5 mg/ml KLH-conjugated peptide into multiple sites of the neck and back skin with at a 2-week interval. Antisera, ...
Source: Frontiers in Neuroanatomy - Category: Neurology Source Type: research
Conclusions: We demonstrated in the SOD1G93A model of ALS that increased levels of several cytokines were associated with a shorter lifespan. However, their role as prognostic biomarkers is unclear as their expression was very variable depending on both the disease stage and the subject. Nevertheless, cytokines may be potential therapeutic targets. Introduction Amyotrophic Lateral Sclerosis (ALS) is one of the most common rare diseases of unknown origin that leads to progressive motor neuron degeneration and muscle denervation (1). In particular, it has been described that either distal axonopathy or neuromuscular ju...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ski A Abstract Neurodegeneration (NDG) is linked with the progressive loss of neural function with intellectual and/or motor impairment. Several diseases affecting older individuals, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, stroke, Multiple Sclerosis and many others, are the most relevant disorders associated with NDG. Since other pathologies such as refractory epilepsy, brain infections, or hereditary diseases such as "neurodegeneration with brain iron accumulation", also lead to chronic brain inflammation with loss of neural cells, NDG can...
Source: Epilepsy Curr - Category: Neurology Authors: Tags: Curr Neuropharmacol Source Type: research
Authors: Ohnishi T, Ohnishi ST, Salerno JC Abstract NADH-quinone oxidoreductase (complex I) is the largest and most complicated enzyme complex of the mitochondrial respiratory chain. It is the entry site into the respiratory chain for most of the reducing equivalents generated during metabolism, coupling electron transfer from NADH to quinone to proton translocation, which in turn drives ATP synthesis. Dysfunction of complex I is associated with neurodegenerative diseases such as Parkinson's and Alzheimer's, and it is proposed to be involved in aging. Complex I has one non-covalently bound FMN, eight to 10 iron-sul...
Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research
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