Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model.
Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model.
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DOI：
10.1038/s41598-018-27626-4
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发表时间：
2018-06-15
影响因子：
4.6
通讯作者：
Kikkawa F
中科院分区：
文献类型：
--
作者：
Imai K;Kotani T;Tsuda H;Nakano T;Ushida T;Iwase A;Nagai T;Toyokuni S;Suzumura A;Kikkawa F
本研究旨在探讨脂多糖（LPS）诱导的母体免疫激活（MIA）模型中后代的长期结局以及母体分子氢（H2）给药的影响。我们之前已经在MIA小鼠模型中证明，母体给药H2可以减轻胎儿大脑中的氧化损伤和神经炎症，包括诱导的促炎细胞因子和小胶质细胞激活。短期记忆、社交能力和社交新颖性以及感觉运动门控分别在出生后3或4周使用y迷宫、三室和脉冲前抑制（PPI）测试进行评估。在出生后5周用免疫组织化学方法分析神经元和少突胶质细胞的数量。暴露于lps的幼鼠的后代在杏仁核和皮质的神经元和少突胶质细胞丧失后，表现出短期记忆和社会互动的缺陷。母体给氢显著减轻了lps诱导的这些异常。此外，我们在体内和体外评估了H2对lps诱导的星形细胞活化的影响。lps暴露小鼠的星形胶质细胞数量增加，而h2给药小鼠的星形胶质细胞数量减少。在原代培养的星形胶质细胞中，lps诱导的促炎性细胞因子被H2抑制。总的来说，这些发现表明，母亲给氢具有神经保护作用，并改善mia诱导的后代以后的神经发育缺陷。
The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H2) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H2 attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks. The number of neurons and oligodendrocytes was also analyzed at postnatal 5 weeks by immunohistochemical analysis. Offspring of the LPS-exposed dams showed deficits in short-term memory and social interaction, following neuronal and oligodendrocytic loss in the amygdala and cortex. Maternal H2 administration markedly attenuated these LPS-induced abnormalities. Moreover, we evaluated the effect of H2 on LPS-induced astrocytic activation, both in vivo and in vitro. The number of activated astrocytes with hypertrophic morphology was increased in LPS-exposed offspring, but decreased in the offspring of H2-administered dams. In primary cultured astrocytes, LPS-induced pro-inflammatory cytokines were attenuated by H2 administration. Overall, these findings indicate that maternal H2 administration exerts neuroprotective effects and ameliorates MIA-induced neurodevelopmental deficits of offspring later in life.
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影响因子：
1.4
作者：
Chlodzinska, Natalia;Gajerska, Monika;Djavadian, Rouzanna L.
通讯作者：
Djavadian, Rouzanna L.
影响因子：
10.6
作者：
Amaral, DG
通讯作者：
Amaral, DG
DOI：
10.3109/10253890.2016.1149695
发表时间：
2016-03-01
影响因子：
2.3
作者：
Izvolskaia, Marina S.;Tillet, Yves;Zakharova, Lyudmila A.
通讯作者：
Zakharova, Lyudmila A.
DOI：
10.1126/science.aag3194
发表时间：
2016-08-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Estes ML;McAllister AK
通讯作者：
McAllister AK
影响因子：
5.3
作者：
Bilbo SD;Block CL;Bolton JL;Hanamsagar R;Tran PK
通讯作者：
Tran PK