Choi Juwon, Kim Yoo Sung, Kim Mi-Hye, Kim Hee Jung, Yoon Bo-Eun
Department of Molecular Biology, College of Natural Sciences, Dankook University, Cheonan, South Korea.
Department of Physiology, College of Medicine, Dankook University, Cheonan, South Korea.
Front Cell Neurosci. 2022 Aug 22;16:954807. doi: 10.3389/fncel.2022.954807. eCollection 2022.
Lead (Pb) is one of the most prevalent heavy metals we encounter daily. Although there are many reports regarding their toxic effects on humans, the effects of exposure to low lead concentrations throughout the pregnancy period on the offspring are not fully elucidated yet. This study aimed to investigate the cellular mechanisms that occur in response to lead exposure. To this end, we administered lead-containing water to pregnant mice from the day of conception till delivery or till day 28 postnatally. Furthermore, we performed neurodevelopmental disorder-related behavior tests and RNA-sequencing analysis. We used both genders for all experiments because neurodevelopmental disorders usually show several sex-dependent differences. The results revealed increased levels of gliosis in the cerebella of lead-exposed pups compared to those in littermates belonging to the control group. Additionally, we observed altered behaviors of male mice in the autism spectrum disorder-related tests. RNA-sequencing results revealed changes in gamma-aminobutyric acid (GABA) signaling in the lead-exposed mouse model. Specifically, the lead-exposed male mice showed decreased monoamine oxidase B and increased levels of diamine oxidase enzyme, which is related to the synthesis of GABA in astrocytes. These findings demonstrate sex-dependent basal developmental changes in glial cells and an increased prevalence of autistic-like behaviors in the young pups of mothers exposed to lead during pregnancy.
铅（Pb）是我们日常接触到的最常见重金属之一。尽管有许多关于其对人类毒性作用的报道，但孕期暴露于低浓度铅对后代的影响尚未完全阐明。本研究旨在探究铅暴露后发生的细胞机制。为此，我们从受孕之日起至分娩或直至产后第28天，给怀孕小鼠饮用含铅水。此外，我们进行了神经发育障碍相关行为测试和RNA测序分析。所有实验均使用了雌雄两性小鼠，因为神经发育障碍通常表现出一些性别依赖性差异。结果显示，与对照组同窝小鼠相比，铅暴露幼崽小脑的胶质细胞增生水平升高。此外，我们在自闭症谱系障碍相关测试中观察到雄性小鼠行为发生改变。RNA测序结果显示，铅暴露小鼠模型中γ-氨基丁酸（GABA）信号传导发生变化。具体而言，铅暴露雄性小鼠单胺氧化酶B水平降低，而二胺氧化酶水平升高，后者与星形胶质细胞中GABA的合成有关。这些发现表明，孕期暴露于铅的母鼠所产幼崽的神经胶质细胞存在性别依赖性基础发育变化，且类似自闭症行为的发生率增加。
