Chiang Yi-Fen, Nguyen Ngan Thi Kim, Hsia Shih-Min, Chen Hsin-Yuan, Lin Shyh-Hsiang, Lin Ching-I
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
Programs of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei 10610, Taiwan.
Biomedicines. 2023 Feb 24;11(3):698. doi: 10.3390/biomedicines11030698.
Hypoglycemia has been known as a potential contributory factor to neurodegenerative diseases, such as Alzheimer's disease. There may be shared pathogenic mechanisms underlying both conditions, and the ketone body, β-hydroxybutyrate (BHB), as an alternative substrate for glucose may exert neuroprotection against hypoglycemia-induced injury. To investigate this, Neuro-2a cells were subjected to a 24 h period of glucose deprivation with or without the presence of BHB. Cell viability, reactive oxygen species (ROS) production, apoptosis, autophagy, and adenosine triphosphate (ATP) and beta-amyloid peptide (Aβ) levels were evaluated. The results show that Neuro-2a cells deprived of glucose displayed a significant loss of cell survival with a corresponding decrease in ATP levels, suggesting that glucose deprivation was neurotoxic. This effect was likely attributed to the diverse mechanisms including raised ROS, defective autophagic flux and reduced basal Aβ levels (particularly monomeric Aβ). The presence of BHB could partially protect against the loss of cell survival induced by glucose deprivation. The mechanisms underlying the neuroprotective actions of BHB might be mediated, at least in part, through restoring ATP, and modulating ROS production, autophagy flux efficacy and the monomeric Aβ level. Results imply that a possible link between the basal monomeric Aβ and glucose deprivation neurotoxicity, and treatments designed for the prevention of energy impairment, such as BHB, may be beneficial for rescuing surviving cells in relation to neurodegeneration.
低血糖一直被认为是神经退行性疾病（如阿尔茨海默病）的一个潜在促成因素。这两种疾病可能存在共同的致病机制，而酮体β-羟基丁酸酯（BHB）作为葡萄糖的替代底物，可能对低血糖诱导的损伤发挥神经保护作用。为了对此进行研究，将Neuro-2a细胞置于有或没有BHB存在的情况下进行24小时的葡萄糖剥夺处理。评估了细胞活力、活性氧（ROS）生成、细胞凋亡、自噬以及三磷酸腺苷（ATP）和β-淀粉样肽（Aβ）水平。结果表明，缺乏葡萄糖的Neuro-2a细胞显示出细胞存活率显著下降，同时ATP水平相应降低，这表明葡萄糖剥夺具有神经毒性。这种效应可能归因于多种机制，包括ROS升高、自噬通量缺陷以及基础Aβ水平降低（特别是单体Aβ）。BHB的存在可以部分保护细胞免受葡萄糖剥夺诱导的细胞存活率损失。BHB神经保护作用的潜在机制可能至少部分是通过恢复ATP、调节ROS生成、自噬通量效率和单体Aβ水平来介导的。结果表明，基础单体Aβ与葡萄糖剥夺神经毒性之间可能存在联系，而针对预防能量损伤设计的治疗方法（如BHB）可能有利于挽救与神经退行性变相关的存活细胞。
