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Exposure to lead on expression levels of brain immunoglobulins, inflammatory cytokines, and brain-derived neurotropic factor in fetal and postnatal mice with autism-like characteristics
Journal of Toxicology and Environmental Health, Part A ( IF 2.3 ) Pub Date : 2021-06-30 , DOI: 10.1080/15287394.2021.1945985
KyeongMin Shin 1 , GyeongDong Lim 1 , Young-Seoub Hong 2 , SoNam Kim 1 , SoRyeon Hwang 1 , JaeHee Lee 1 , SoJung Sin 1 , AhRang Cho 1 , YeonGyeong Kim 1 , Ravi Gautam 1 , JiHun Jo 1 , Manju Acharya 1 , Anju Maharjan 1 , DaEun Lee 1 , Pramod B K C 3 , ChangYul Kim 3 , Yong Heo 1, 3 , Hyoung-Ah Kim 4
Affiliation  

ABSTRACT

Autism spectrum disorders (ASD) are neurodevelopmental disorders, and their incidence is increasing worldwide. Increased exposure to environmental metal lead (Pb) has been proposed as a risk factor associated with ASD. In the present study, BTBR T+ tf/J (BTBR) mice with ASD-like behavioral characteristics and control FVB mice were exposed gestationally and/or neonatally to Pb, and compared with highly social FVB mice to investigate neuroimmunological abnormalities. IgG1 and IgG2a levels in fetal brains from BTBR dams exposed to Pb (BTBR-Pb) were significantly higher than those of BTBR-controls (BTBR-C). However, this change did not occur in FVB mice exposed to Pb. The IgG1:IgG2a ratio was higher in both fetal and postnatal brains of BTBR mice compared to FVB animals regardless of Pb exposure. The IL-4:IFN-γ ratio was elevated in BTBR-Pb relative to BTBR-C mice, but this ratio was not markedly affected following Pb exposure in FVB animals. These findings suggest the potential for a Pb-driven predominant TH2-like reactivity profile in brain microenvironment present in BTBR mice. Brain-derived neurotrophic factor was decreased in fetal and postnatal BTBR-Pb brains relative to BTBR-C brains but not in FVB-Pb relative to FVB-C mice. Taken together, data demonstrate that Pb exposure might contribute to developmental brain abnormalities associated with ASD, particularly in individuals with genetic susceptibility to ASD.



中文翻译:

铅暴露对具有自闭症样特征的胎儿和出生后小鼠的脑免疫球蛋白、炎性细胞因子和脑源性神经营养因子的表达水平的影响

摘要

自闭症谱系障碍 (ASD) 是神经发育障碍,其发病率在全球范围内不断增加。增加暴露于环境金属铅 (Pb) 已被认为是与 ASD 相关的风险因素。在本研究中,BTBR T+  tf具有 ASD 样行为特征的 /J (BTBR) 小鼠和对照 FVB 小鼠在妊娠期和/或新生儿期暴露于铅,并与高度社交的 FVB 小鼠进行比较以研究神经免疫异常。来自暴露于 Pb 的 BTBR 母猪(BTBR-Pb)的胎儿大脑中的 IgG1 和 IgG2a 水平显着高于 BTBR 对照组(BTBR-C)。然而,这种变化在暴露于 Pb 的 FVB 小鼠中没有发生。与 FVB 动物相比,BTBR 小鼠的胎儿和出生后大脑中的 IgG1:IgG2a 比率更高,无论是否接触铅。与 BTBR-C 小鼠相比,BTBR-Pb 中的 IL-4:IFN-γ 比率升高,但在 FVB 动物中接触 Pb 后,该比率并未受到显着影响。这些发现表明 Pb 驱动的主要 T H的潜力BTBR 小鼠大脑微环境中的 2 样反应性特征。相对于 BTBR-C 大脑,胎儿和出生后 BTBR-Pb 大脑中的脑源性神经营养因子降低,但相对于 FVB-C 小鼠,FVB-Pb 中的脑源性神经营养因子降低。总之,数据表明铅暴露可能导致与 ASD 相关的大脑发育异常,特别是在具有 ASD 遗传易感性的个体中。

更新日期:2021-08-26
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