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بدون خلاصۀ ویرایش |
بدون خلاصۀ ویرایش |
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| خط ۱۴: | خط ۱۴: | ||
The Improvement of Energy Metabolism in the Central Nervous System | The Improvement of Energy Metabolism in the Central Nervous System | ||
Autism spectrum disorder individuals have impaired mitochondrial energy production due to the presence of abnormal mitochondrial markers in their plasma, such as elevated levels of lactic acid and pyruvate. Weissman et al. showed that Autism spectrum disorder patients had mitochondrial electron transport chain dysfunction, including complex I and complex III deficiencies. A ketogenic diet provides fuel sources in the human body, and the ketone bodies, including β-hydroxybutyrate, cross the blood-brain barrier and replace glucose as fuel for the brain. This molecule crosses the blood-brain barrier via proton symporters and a sodium-dependent monocarboxylate transporter, which is located in the blood-brain barrier, neurons, and astrocytes. Ketone bodies enhance adenosine triphosphate (ATP) production via the Krebs cycle to generate energy and balance metabolism. A ketogenic diet reduced seizures by enhancing brain metabolism via the regulation of transcripts encoding energy metabolism enzymes or mitochondrial proteins in rats with seizures. | Autism spectrum disorder individuals have impaired mitochondrial energy production due to the presence of abnormal mitochondrial markers in their plasma, such as elevated levels of lactic acid and pyruvate. Weissman et al. showed that Autism spectrum disorder patients had mitochondrial electron transport chain dysfunction, including complex I and complex III deficiencies. A ketogenic diet provides fuel sources in the human body, and the ketone bodies, including β-hydroxybutyrate, cross the blood-brain barrier and replace glucose as fuel for the brain. This molecule crosses the blood-brain barrier via proton symporters and a sodium-dependent monocarboxylate transporter, which is located in the blood-brain barrier, neurons, and astrocytes. Ketone bodies enhance adenosine triphosphate (ATP) production via the Krebs cycle to generate energy and balance metabolism. A ketogenic diet reduced seizures by enhancing brain metabolism via the regulation of transcripts encoding energy metabolism enzymes or mitochondrial proteins in rats with seizures. | ||
Anti-inflammatory Activity and Antioxidative Stress | |||
One of the risk factors for Autism spectrum disorder in children is abnormal maternal immune activation. For example, pregnant mice were injected with double-stranded RNA (dsRNA) poly (I: C) to mimic a viral infection, and the offspring of these mice had Autism spectrum disorder-like behaviors. Autism spectrum disorder patients also experience aberrant inflammation. Some cytokines and chemokines, such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and monocyte chemotactic protein-1, are found at abnormal levels in brain samples and cerebrospinal fluid in Autism spectrum disorder patients. These cytokines activate the immune response via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Young and colleagues found that the NF-κB protein was hyper-expressed in mature microglia in brain samples in Autism spectrum disorder patients, which indicates that immunity is activated in the brains of Autism spectrum disorder patients. Autism spectrum disorder patients also had higher levels of eight cytokines in plasma compared to control individuals. Autism spectrum disorder individuals also have associated oxidative stress level upregulation and antioxidant ability downregulation. Evidence showed that antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, are altered in Autism spectrum disorder patients, which increases inflammation. In summary, there is a consensus that Autism spectrum disorder individuals have immune dysfunction. | |||
A ketogenic diet has powerful anti-inflammatory activity and antioxidative stress effects in the brain. Jeong et al. found that a ketogenic diet reduced neuroinflammation via the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) and protected against excitotoxicity-induced neuronal cell death. Fatty acids activate PPARs and are critical regulators of lipid metabolism. Greco et al. found that ketone bodies decreased oxidative stress and improved the mitochondrial respiratory complex activity in a traumatic brain injury animal model. A ketogenic diet likely normalizes mitochondrial function by stimulating mitochondrial biogenesis, decreasing oxidative stress and the levels of pro-apoptotic factors, preventing changes in mitochondrial permeability, and decreasing the mitochondrial ROS production in neocortical neurons. Mirza et al. showed that rats treated with propionic acid exhibited social impairment and repetitive behavior. The cerebellum, brainstem, and prefrontal cortex of these rats had high levels of oxidative stress and inflammation, with increased IL-6 and TNF-α levels and decreased IL-10 levels. They also found that decreased levels of oxidative stress and inflammation improved neurobehavioral disorders in rats. | |||