Department of Neuroanatomy, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland.
Department of Neuroanatomy, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland.
Neuroscience. 2019 Aug 10;413:239-251. doi: 10.1016/j.neuroscience.2019.06.009. Epub 2019 Jun 18.
Ketogenic diet is reported to protect against cognitive decline, drug-resistant epilepsy, Alzheimer's Disease, damaging effect of ischemic stroke and many neurological diseases. Despite mounting evidence that this dietary treatment works, the exact mechanism of its protective activity is largely unknown. Ketogenic diet acts systemically, not only changing GABA signaling in neurons, but also influencing the reliance on mitochondrial respiration, known to be disrupted in many neurological diseases. Normally, human body is driven by glucose while ketogenic diet mimics starvation and energy required for proper functioning comes from fatty acids oxidation. In the brain astrocytes are believed to be the sole neural cells capable of fatty oxidation. Here we try to explain that not exclusively neurons, but also morphological changes of astroglia and/or microglia due to different metabolic state are important for the mechanism underlying the protective role of ketogenic diet. By quantifying different parameters describing cellular morphology like ramification index or fractal dimension and using Principal Component Analysis to discover the regularities between them, we demonstrate that in normal adult rat brain, ketogenic diet itself is able to change glial morphology, indicating an important role of these underappreciated cells in the brain metabolism.
生酮饮食被报道能预防认知能力下降、耐药性癫痫、阿尔茨海默病、缺血性中风的损伤作用和许多神经疾病。尽管越来越多的证据表明这种饮食治疗有效，但它的保护活性的确切机制在很大程度上尚不清楚。生酮饮食不仅全身性地改变神经元中的 GABA 信号，还影响对线粒体呼吸的依赖，已知许多神经疾病中线粒体呼吸会受到干扰。正常情况下，人体依赖葡萄糖，而生酮饮食模拟饥饿，而适当功能所需的能量来自脂肪酸氧化。在大脑中，星形胶质细胞被认为是唯一能够进行脂肪酸氧化的神经细胞。在这里，我们试图解释，不仅神经元，而且星形胶质细胞和/或小胶质细胞的形态变化，由于不同的代谢状态，对于生酮饮食保护作用的机制也是重要的。通过量化描述细胞形态的不同参数，如分支指数或分形维数，并使用主成分分析来发现它们之间的规律，我们证明在正常成年大鼠大脑中，生酮饮食本身就能改变神经胶质的形态，这表明这些被低估的细胞在大脑代谢中起着重要作用。
