The microbiota influences cell death and microglial colonization in the perinatal mouse brain.
The microbiota influences cell death and microglial colonization in the perinatal mouse brain.
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DOI：
10.1016/j.bbi.2017.08.027
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Forger NG
中科院分区：
文献类型：
--
作者：
Castillo-Ruiz A;Mosley M;George AJ;Mussaji LF;Fullerton EF;Ruszkowski EM;Jacobs AJ;Gewirtz AT;Chassaing B;Forger NG
哺乳动物胎儿在无菌环境中发育，直到出生才直接暴露于复杂的微生物群。我们利用这一点来研究微生物群在生命最初几天对大脑发育的影响。在新生的常规定植小鼠和在无菌、无菌（GF）条件下出生的小鼠之间比较了抗炎和促炎细胞因子的表达、发育性细胞死亡和脑中的小胶质细胞定植。促炎细胞因子白细胞介素1β和肿瘤坏死因子α在GF新生儿中的表达明显受到抑制。GF小鼠的细胞死亡也发生了改变，一些区域表现出较高的细胞死亡率（下丘脑的室旁核和海马的CA 1定向层），而其他区域表现出无变化或较低的细胞死亡率（下丘脑的弓状核）。GF小鼠中小胶质细胞标记升高，这是由于小胶质细胞大小和数量增加。细胞因子表达、细胞死亡和小胶质细胞标记的变化在出生当天是明显的，但在胚胎第18.5天，即预期分娩前约半天不存在。总的来说，我们的研究结果表明，出生时直接接触微生物群会影响关键的神经发育事件，并在几小时内完成。这些发现可能有助于解释以前在成年GF小鼠中观察到的一些行为和神经化学变化。
The mammalian fetus develops in a largely sterile environment, and direct exposure to a complex microbiota does not occur until birth. We took advantage of this to examine the effect of the microbiota on brain development during the first few days of life. The expression of anti- and pro-inflammatory cytokines, developmental cell death, and microglial colonization in the brain were compared between newborn conventionally colonized mice and mice born in sterile, germ-free (GF) conditions. Expression of the pro-inflammatory cytokines interleukin 1β and tumor necrosis factor α was markedly suppressed in GF newborns. GF mice also had altered cell death, with some regions exhibiting higher rates (paraventricular nucleus of the hypothalamus and the CA1 oriens layer of the hippocampus) and other regions exhibiting no change or lower rates (arcuate nucleus of the hypothalamus) of cell death. Microglial labeling was elevated in GF mice, due to an increase in both microglial cell size and number. The changes in cytokine expression, cell death and microglial labeling were evident on the day of birth, but were absent on embryonic day 18.5, approximately one-half day prior to expected delivery. Taken together, our results suggest that direct exposure to the microbiota at birth influences key neurodevelopmental events and does so within hours. These findings may help to explain some of the behavioral and neurochemical alterations previously seen in adult GF mice.
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DOI：
10.1523/jneurosci.2102-11.2011
发表时间：
2011-09-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Faustino JV;Wang X;Johnson CE;Klibanov A;Derugin N;Wendland MF;Vexler ZS
通讯作者：
Vexler ZS
影响因子：
64.8
作者：
Chassaing B;Koren O;Goodrich JK;Poole AC;Srinivasan S;Ley RE;Gewirtz AT
通讯作者：
Gewirtz AT
影响因子：
2.5
作者：
Ahern, Todd H.;Krug, Stefanie;Forger, Nancy G.
通讯作者：
Forger, Nancy G.
DOI：
10.1073/pnas.1002601107
发表时间：
2010-06-29
影响因子：
11.1
作者：
Dominguez-Bello, Maria G.;Costello, Elizabeth K.;Knight, Rob
通讯作者：
Knight, Rob
影响因子：
5.5
作者：
Dilger, Ryan N.;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.