Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Biol Trace Elem Res. 2021 Nov;199(11):4193-4204. doi: 10.1007/s12011-020-02553-6. Epub 2021 Jan 5.
Maternal immune activation (MIA) model has been profoundly described as a suitable approach to study the pathophysiological mechanisms of neuropsychiatric disorders, including schizophrenia. Our previous study revealed that prenatal exposure to lipopolysaccharide (LPS) induced working memory impairments in only male offspring. Based on the putative role of prefrontal cortex (PFC) in working memory process, the current study was conducted to examine the long-lasting effect of LPS-induced MIA on several neuroinflammatory mediators in the PFC of adult male pups. We also investigated whether maternal zinc supplementation can alleviate LPS-induced alterations in this region. Pregnant rats received intraperitoneal injections of either LPS (0.5 mg/kg) or saline on gestation days 15/16 and supplemented with ZnSO4 (30 mg/kg) throughout pregnancy. At postnatal day 60, the density of both microglia and astrocyte cells and the expression levels of IL-6, IL-1β, iNOS, TNF-α, NF-κB, and GFAP were evaluated in the PFC of male pups. Although maternal LPS treatment increased microglia and astrocyte density, number of neurons in the PFC of adult offspring remained unchanged. These findings were accompanied by the exacerbated mRNA levels of IL-6, IL-1β, iNOS, TNF-α, NF-κB, and GFAP as well. Conversely, prenatal zinc supplementation alleviated the mentioned alterations induced by LPS. These findings support the idea that the deleterious effects of prenatal LPS exposure could be attenuated by zinc supplementation during pregnancy. It is of interest to suggest early therapeutic intervention as a valuable approach to prevent neurodevelopmental deficits, following maternal infection. Schematic diagram describing the experimental timeline. On gestation days (GD) 15 and 16, pregnant dams were administered with intraperitoneal injections of either LPS (0.5 mg/kg) or vehicle and supplemented with ZnSO4 (30 mg/kg) throughout pregnancy by gavage. The resulting offspring were submitted to qPCR, immunostaining, and morphological analysis at PND 60. Maternal zinc supplementation alleviated increased expression levels of inflammatory mediators and microglia and astrocyte density induced by LPS in the PFC of treated offspring. PND postnatal day, PFC prefrontal cortex.
母体免疫激活 (MIA) 模型已被深入描述为研究神经精神疾病病理生理机制的合适方法，包括精神分裂症。我们之前的研究表明，产前暴露于脂多糖 (LPS) 仅会导致雄性后代出现工作记忆障碍。基于前额叶皮层 (PFC) 在工作记忆过程中的假定作用，本研究旨在检查 LPS 诱导的 MIA 对成年雄性幼仔 PFC 中几种神经炎症介质的长期影响。我们还研究了母体补锌是否可以减轻该区域 LPS 诱导的改变。妊娠大鼠在妊娠第 15/16 天腹腔注射 LPS（0.5mg/kg）或生理盐水，并在整个孕期补充 ZnSO4（30mg/kg）。在出生后 60 天，评估雄性幼仔 PFC 中小胶质细胞和星形胶质细胞的密度以及 IL-6、IL-1β、iNOS、TNF-α、NF-κB 和 GFAP 的表达水平。尽管母体 LPS 处理增加了小胶质细胞和星形胶质细胞的密度，但成年后代 PFC 中的神经元数量保持不变。这些发现伴随着 IL-6、IL-1β、iNOS、TNF-α、NF-κB 和 GFAP 的 mRNA 水平加剧。相反，产前补锌减轻了 LPS 引起的上述变化。这些发现支持以下观点，即产前 LPS 暴露的有害影响可以通过孕期补锌来减轻。有趣的是，建议早期治疗干预作为一种有价值的方法，以防止母体感染后神经发育缺陷。描述实验时间线的示意图。在妊娠第 15 和 16 天，给怀孕的母鼠腹腔注射 LPS（0.5mg/kg）或载体，并通过灌胃在整个孕期补充 ZnSO4（30mg/kg）。处理后的后代在 PND60 时进行 qPCR、免疫染色和形态分析。母体补锌减轻了 LPS 诱导的 PFC 中炎症介质和小胶质细胞和星形胶质细胞密度增加的表达水平。PND 出生后天数，PFC 前额叶皮层。
