Zhao Yanling, Pan Xiaoli, Zhao Jing, Wang Yang, Peng Yun, Zhong Chunjiu
Department of Neurology, Zhongshan Hospital & Shanghai Medical College, Fudan University, Shanghai, China.
J Neurochem. 2009 Oct;111(2):537-46. doi: 10.1111/j.1471-4159.2009.06341.x. Epub 2009 Aug 13.
Thiamine deficiency (TD) impairs hippocampal neurogenesis. However, the mechanisms involved are not identified. In this work, TD mouse model was generated using a thiamine-depleted diet at two time points, TD9 and TD14 for 9 and 14 days of TD respectively. The activities of pyruvate dehydrogenase (PDH), alpha-ketoglutamate dehydrogenase (KGDH), glucose-6-phosphate dehydrogenase (G6PD), and transketolase (TK), as well as on the contents of NADP(+) and NADPH were determined in whole mouse brain, isolated cortex, and hippocampus of TD mice model. The effects of TK silencing on the growth and migratory ability of cultured hippocampal progenitor cells (HPC), as well as on neuritogenesis of hippocampal neurons were explored. The results showed that TD specifically reduced TK activity in both cortex and hippocampus, without significantly affecting the activities of PDH, KGDH, and G6PD in TD9 and TD14 groups. The level of whole brain and hippocampal NADPH in TD14 group were significantly lower than that of control group. TK silencing significantly inhibited the proliferation, growth, and migratory abilities of cultured HPC, without affecting neuritogenesis of cultured hippocampal neurons. Taken together, these results demonstrate that decreased TK activity leads to pentose-phosphate pathway dysfunction and contributes to impaired hippocampal neurogenesis induced by TD. TK and pentose-phosphate pathway may be considered new targets to investigate hippocampal neurogenesis.
硫胺素缺乏（TD）会损害海马神经发生。然而，其中涉及的机制尚未明确。在本研究中，通过在两个时间点采用硫胺素缺乏饮食构建TD小鼠模型，分别为TD9和TD14，即硫胺素缺乏9天和14天。测定了TD小鼠模型全脑、分离的皮质和海马中丙酮酸脱氢酶（PDH）、α-酮戊二酸脱氢酶（KGDH）、葡萄糖-6-磷酸脱氢酶（G6PD）和转酮醇酶（TK）的活性，以及NADP(+)和NADPH的含量。探讨了TK沉默对培养的海马祖细胞（HPC）生长和迁移能力以及海马神经元神经突形成的影响。结果显示，TD特异性降低了皮质和海马中的TK活性，而在TD9和TD14组中未显著影响PDH、KGDH和G6PD的活性。TD14组全脑和海马的NADPH水平显著低于对照组。TK沉默显著抑制了培养的HPC的增殖、生长和迁移能力，但不影响培养的海马神经元的神经突形成。综上所述，这些结果表明TK活性降低导致磷酸戊糖途径功能障碍，并导致TD诱导的海马神经发生受损。TK和磷酸戊糖途径可能被视为研究海马神经发生的新靶点。
