Maternal hyperglycemia disturbs neocortical neurogenesis via epigenetic regulation in C57BL/6J mice
Maternal hyperglycemia disturbs neocortical neurogenesis via epigenetic regulation in C57BL/6J mice
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母体高血糖通过表观遗传调控干扰 C57BL/6J 小鼠的新皮质神经发生
DOI：
10.1038/s41419-019-1438-z
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发表时间：
2019-03-01
影响因子：
9
通讯作者：
Hao, Aijun
中科院分区：
文献类型：
--
作者：
Ji, Shufang;Zhou, Wenjuan;Hao, Aijun
妊娠期高血糖母亲的后代比正常妊娠的后代有更高的长期神经精神疾病发生率，这表明新皮质神经发生可能受到母亲高血糖的影响。目前缺乏评估高血糖对神经干细胞新皮层神经遗传分化影响的研究，其机制尚不清楚。我们试图探讨母体高血糖在神经干细胞新皮层神经发生分化中的作用及其可能的分子机制。我们建立了高血糖妊娠小鼠模型，研究宫内暴露于母体高血糖对新皮质神经发生的影响。我们观察了受高糖影响的后代新皮质的形态学变化，并检测了神经干细胞的神经遗传分化。我们研究了高血糖条件下分化神经干细胞中表观遗传修饰和转录因子之间的调控网络。在一些没有畸形的后代中，母亲的高血糖会扰乱新皮质层压。我们的研究结果表明，高血糖通过促进神经干细胞的早期分化，改变了早期出生的神经元的命运和新生神经元在深层的分布。组蛋白乙酰化的改变及其对前神经基因转录的调控可能与神经干细胞分化受阻和新生投射神经元在新皮层的分布改变有关。我们的数据提出了一种可能性，即妊娠期母亲高血糖通过表观遗传调控神经干细胞分化和新皮质神经元的诞生，扰乱了一些未畸形后代的新皮质投射神经元的层流分布。
Offspring of mothers with hyperglycemia during pregnancy have a higher incidence of long-term neuropsychiatric disorders than offspring from a normal pregnancy, indicating that neocortical neurogenesis might be affected by maternal hyperglycemia. A paucity of study evaluating the effects of hyperglycemia on neocortical neurogenetic differentiation of neural stem cells, and the mechanism remains unclear. We sought to investigate the the roles and possible molecular mechanism of maternal hyperglycemia on neocortical neurogenetic differentiation of neural stem cells. We established a mouse model of a hyperglycemic pregnancy to study effects of intrauterine exposure to maternal hyperglycemia on neocortical neurogenesis. We observed morphological changes in the neocortex and detected the neurogenetic differentiation of neural stem cells in offspring affected by high glucose levels. We investigated the regulatory network between epigenetic modification and transcription factors in differentiated neural stem cells under hyperglycemic conditions. Maternal hyperglycemia disturbs neocortical lamination in some non-malformed offspring. Our results suggested that hyperglycemia altered the early-born neuron fate and the distribution of newborn neurons in deep layers by promoting the earlier differentiation of neural stem cells. Altered histone acetylation and its regulation on the transcription of proneural genes might be correlated to the disrupted differentiation of neural stem cells and altered distribution of newborn projection neurons in the neocortex. Our data raised the possibility that maternal hyperglycemia in pregnancy disturbs the laminar distribution of neocortical projection neurons in some non-malformed offspring via epigenetic regulation on neural stem cell differentiation and the birthdate of neocortical neurons.