![]() ![]() The loss of butyrate has a critical role in the health of neurons and targeting this loss reduced or prevented neuropathology. These studies implicate the GM in the CNS pathology of neurological-related diseases. Macrophages treated with Epalrastat, an AR inhibitor, showed reduced CNS inflammatory gene expression in response to LPS, indicating the role of AR in LPS-induced inflammation. While microglial activation remained the same, a significant reduction in macrophage-related cytokines was observed. The brains and livers of AR knock-out mice (ARKO) showed markedly reduced inflammation. Lipopolysaccharide (LPS) was injected intraperitoneally in mice to mimic endotoxemia. Biproducts of this pathway yield increases in inflammatory products and decreases in antioxidants. Aldose reductase (AR) is the rate-limiting enzyme in the polyol pathway. Functionally, cognitive decline was ameliorated in butyrate-supplemented mice. Butyrate supplementation did positively impact inflammation, oxidative stress, and neurofibrillary tangle formation. At 12 months these mice developed dysbiosis, characterized by the loss of butyrate-producing bacteria. The AD 3xTg mouse model was assessed for the development of dysbiosis. Targeting the loss of butyrate reduced the ERSR as well as low-grade inflammation. ![]() In the cerebellum, Purkinje cells were specifically affected. Minimal neuroinflammation occurred in AH-FMT mice, but significant increases in the endoplasmic reticulum stress response (ERSR) across the majority of neurons in the prefrontal cortex and hippocampus were observed. Therefore, we developed a novel mouse model of fecal matter transplantation (FMT) utilizing the microbiome from alcoholic hepatitis (AH) patients, characterized by a loss of butyrogenic potential. Ethanol-related neuropathologies and Alzheimer’s disease (AD) currently have no effective clinical treatment. There is growing evidence that the health of the gut microbiome (GM) has an important role on multiple host organ systems. ![]()
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