Murine maternal dietary restriction affects neural Humanin expression and cellular profile.

Murine maternal dietary restriction affects neural Humanin expression and cellular profile.
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鼠产妇饮食限制会影响神经人类的表达和细胞谱。

DOI:
10.1002/jnr.24568
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发表时间:
2020-05
影响因子:
4.2
通讯作者:
Devaskar SU
Devaskar SU
中科院分区:
医学3区
文献类型:
--
作者:
Baldauf C;Sondhi M;Shin BC;Ko YE;Ye X;Lee KW;Devaskar SU

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为了解宫内生长受限(IUGR)对神经发育影响的细胞基础,我们检测了小鼠(Mus musculus)胎脑内各种细胞类型的整体和区域表达。我们的模型采用从妊娠第10 - 19天母体热量限制为每日食物摄入量的50%,产生IUGR后代。后代头部较小,头身比更大,表明存在头部优先的IUGR效应。通过免疫荧光定量分析,胚胎第19天(E19)的IUGR胎儿巢蛋白(祖细胞)、β - III微管蛋白(未成熟神经元)、胶质纤维酸性蛋白(星形胶质细胞)和O4(少突胶质细胞)细胞谱系减少,皮质厚度减少30%。对照组和IUGR组之间在Bcl - 2或Bax(细胞凋亡)方面未发现差异,不过从定性上看,双皮质素(迁移)和Ki67(增殖)免疫反应性降低。为了研究一种潜在的治疗性肽,我们接下来研究了新型促存活肽——小鼠人源蛋白(mHN)。个体发育检测显示E19时mHN表达最高,到出生后第15天(P15)降低,在成年(3个月)时几乎消失。按性别对mHN表达进行亚分析发现,胎儿期雄性mHN表达较高,出生后性别间无显著差异。此外,与各自对照组相比,IUGR雌性胎儿皮质mHN的增加幅度大于雄性胎儿。我们得出结论,母体饮食限制相关的IUGR会干扰神经祖细胞分化为构成大脑皮质的各种细胞成分,并减小大脑皮质的大小。mHN的表达具有发育阶段和性别特异性,在IUGR情况下,特别是在雌性中,其表达适应性增加,以介导一种对抗营养逆境的促存活途径。
To understand the cellular basis for the neurodevelopmental effects of intra-uterine growth restriction (IUGR), we examined global and regional expression of various cell types within murine (Mus musculus) fetal brain. Our model employed maternal calorie restriction to 50% daily food intake from gestation day 10-19, producing IUGR offspring. Offspring had smaller head sizes with larger head:body ratios indicating a head sparing IUGR effect. IUGR fetuses at embryonic day 19 (E19) had reduced nestin (progenitors), β-III Tubulin (immature neurons), GFAP (astrocytes), and O4 (oligodendrocytes) cell lineages via immunofluorescence quantification and a 30% reduction in cortical thickness. No difference was found in Bcl-2 or Bax (apoptosis) between controls and IUGR, though qualitatively, doublecortin (migration) and Ki67 (proliferation) immunoreactivity were decreased. In the interest of examining a potential therapeutic peptide, we next investigated novel pro-survival peptide, mouse Humanin (mHN). Ontogeny examination revealed highest mHN expression at E19, diminishing by post-natal day 15 (P15) and nearly absent in adult (3 month). Sub-analysis by sex for mHN expression yielded higher mHN expression among males during fetal life, without significant difference between sexes post-natally. Further, IUGR had a greater increase in cortical mHN in the female versus the male fetus over their respective controls. We conclude that maternal dietary restriction associated IUGR interferes with neural progenitors differentiating into the various cellular components populating the cerebral cortex and reduces cerebral cortical size. mHN expression is developmental stage and sex specific, with IUGR, particularly in the females, adaptively increasing its expression towards mediating a pro-survival approach against nutritional adversity.
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