Department of Food and Nutrition, Seoul National University, Seoul 08826, Republic of Korea; Research Institute of Human Ecology, Seoul National University, Seoul 08826, Republic of Korea.
Department of Food Science and Nutrition & the Korean Institute of Nutrition, Hallym University, Chuncheon, Gwangwon-do 24252, Republic of Korea.
Life Sci. 2022 Nov 15;309:121041. doi: 10.1016/j.lfs.2022.121041. Epub 2022 Oct 5.
It is well known that a low-status of B vitamins is associated with cognitive impairment. However, the impact of vitamin B6 (VB6) restriction on neurodegenerative diseases and its underlying mechanisms are rarely understood. This study investigated whether VB6 restriction aggravates neurodegeneration in mice fed either a low-fat (LF) control diet or a high-fat (HF) diet.
Six-week-old male C57BL/6J mice were divided into 4 groups (LF7, LF1, HF7 and HF1) and fed either an LF diet [7 mg pyridoxine (PN)/kg diet], an LF with 1 mg PN/kg diet, an HF diet or an HF with 1 mg PN/kg diet for 16 weeks. Brain cortex and hippocampus were collected and used for the determination of biochemical parameters including VB6, lipid peroxides, and neurodegeneration-related mRNA and protein levels.
VB6 restriction reduced levels of the biologically active form of VB6, pyridoxal phosphate (PLP) in the brain. Low consumption of VB6 inactivated brain-derived neurotrophic factor signaling and cell proliferation, and induced oxidative stress, endoplasmic reticulum stress and apoptotic cell death. Significant correlation between brain lipid peroxide levels and PLP levels were observed. VB6 restriction also induced characteristic features of neurodegeneration such as amyloid-β deposition and tau hyperphosphorylation. Similarly, high-fat diet increased parameters associated with neurodegeneration. Aggravating effects of VB6 restriction were observed in both LF control and HF groups.
Dietary VB6 restriction plays a key role in neurodegeneration, and VB6 restriction worsens HF-induced neuronal damage in mice. Our study emphasizes the essential role of VB6 in maintaining brain health.
众所周知，B 族维生素水平低与认知障碍有关。然而，VB6 限制对神经退行性疾病的影响及其潜在机制很少被了解。本研究旨在探讨 VB6 限制是否会加重低脂（LF）对照饮食或高脂（HF）饮食喂养的小鼠的神经退行性病变。
将 6 周龄雄性 C57BL/6J 小鼠分为 4 组（LF7、LF1、HF7 和 HF1），并分别喂食 LF 饮食[7mg 吡哆醇（PN）/kg 饮食]、LF 加 1mg PN/kg 饮食、HF 饮食或 HF 加 1mg PN/kg 饮食 16 周。收集大脑皮质和海马体，用于测定 VB6、脂质过氧化物和与神经退行性变相关的 mRNA 和蛋白水平等生化参数。
VB6 限制降低了大脑中生物活性形式 VB6（吡哆醛 5-磷酸，PLP）的水平。VB6 低消耗使脑源性神经营养因子信号和细胞增殖失活，并诱导氧化应激、内质网应激和凋亡细胞死亡。观察到大脑脂质过氧化物水平与 PLP 水平之间存在显著相关性。VB6 限制还诱导了神经退行性变的特征性特征，如淀粉样蛋白-β沉积和 tau 过度磷酸化。同样，高脂饮食增加了与神经退行性变相关的参数。在 LF 对照组和 HF 组中均观察到 VB6 限制的加重作用。
饮食 VB6 限制在神经退行性变中起关键作用，VB6 限制加重了 HF 诱导的小鼠神经元损伤。我们的研究强调了 VB6 在维持大脑健康中的重要作用。
