Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model
Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model
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DOI：
10.1016/j.bbr.2019.112247
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发表时间：
2020-01-13
影响因子：
2.7
通讯作者：
Shaerzadeh, Fatemeh
中科院分区：
文献类型：
--
作者：
Alizadeh, Faezeh;Davoodian, Nahid;Shaerzadeh, Fatemeh
母亲在怀孕期间感染被认为是后代患精神分裂症的一个关键危险因素。有证据表明，母亲暴露于感染性病原体与胎儿缺锌有关。由于锌在脑功能和发育中的重要作用，本研究以脂多糖（LPS）作为精神分裂症的模型，激活母体免疫系统，以研究孕期补锌是否能逆转LPS诱导的有害效应，以验证这一假设。孕鼠腹腔注射生理盐水或LPS在妊娠第15天和第16天给予0.5 mg/kg锌，在整个妊娠期间通过灌胃给予锌补充剂（30 mg/kg）。在出生后60天，Y-迷宫评估后代的工作记忆。此外，儿茶酚O-甲基转移酶（COMT）和谷氨酸脱羧酶67（GAD 67）的表达水平的大脑样本中，只有男性后代产前暴露于LPS显示出显着的损害的工作记忆。此外，产前LPS暴露导致雄性幼仔GAD 67表达水平中度下降，而COMT表达无变化。有趣的是，补锌恢复了雄性大鼠工作记忆和GAD 67 mRNA水平的改变。母鼠子代的工作记忆和COMT/GAD 67基因表达均未发生改变，说明孕期补锌可减轻LPS对雄性仔鼠的损伤。这些结果支持在怀孕期间补充锌以限制后代感染引起的神经发育缺陷的想法。
Maternal infection during pregnancy is considered a key risk factor for developing schizophrenia in offspring. There is evidence that maternal exposure to infectious agents is associated with fetal zinc deficiency. Due to the essential role of zinc in brain function and development, in the present study, we activated maternal immune system using lipopolysaccharide (LPS) as a model of schizophrenia to examine whether zinc supplementation throughout pregnancy can reverse LPS-induced deleterious effects.To test the hypothesis, pregnant rats were treated with intraperitoneal injection of either saline or LPS (0.5 mg/kg) at gestational day 15 and 16, and zinc supplementation (30 mg/kg) was administered throughout pregnancy by gavage. At postnatal day 60, Y-maze was used to evaluate working memory of offspring. Moreover, the expression levels of catechol O-methyltransferase (COMT) and glutamate decarboxylase 67 (GAD67) were measured in the frontal cortex of the brain samples.Only male offspring prenatally exposed to LPS showed a significant impairment in working memory. In addition, prenatal LPS exposure causes a moderate decrease in GAD67 expression level in the male pups, while COMT expression was found unchanged. Interestingly, zinc supplementation restored the alterations in working memory as well as GAD67 mRNA level in the male rats. No alteration was detected for neither working memory nor COMT/GAD67 genes expression in female offspring.This study demonstrates that zinc supplementation during pregnancy can attenuate LPS-induced impairments in male pups. These results support the idea to consume zinc supplementation during pregnancy to limit neurodevelopmental deficits induced by infections in offspring.