Cao Can, Li Jian, Cui Wenqi, Dai Jiaohua, Guan Zhiyu, Wang Dan, Zhao Xiujuan
School of Public Health, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, Heilongjiang, China.
Biol Trace Elem Res. 2024 Dec 28. doi: 10.1007/s12011-024-04501-0.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder emerging during early childhood. However, the mechanism underlying the pathogenesis of ASD remains unclear. This study investigated the alterations of elements in serum and prefrontal cortex of BTBR T + tf/J (BTBR) mice and potential mechanisms. The male BTBR mice were used for experimental group and C57BL/6 J (C57) mice were used for control group (n = 15). After behavioral tests were monitored, serum and prefrontal cortex of mice were analyzed by ICP-MS. The results demonstrated that the level of copper (Cu) was increased, and the levels of calcium (Ca), magnesium (Mg), selenium (Se), cobalt (Co), iron (Fe) and zinc (Zn) were decreased in BTBR mice compared to C57 mice (p < 0.01). The levels of above differential elements in serum demonstrated positive correlations with those in prefrontal cortex. Meanwhile, differential elements in prefrontal cortex had correlations with the total distance traveled (open field test) and the number of marbles buried (marble burying test) in BTBR mice (p < 0.05 or p < 0.01). The abnormally changed elements in serum might cross blood-brain-barrier into the brain and lead to oxidative stress, causing inflammation. Furtherly, the levels of inflammation-related indicators including tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were increased in prefrontal cortex of BTBR mice (p < 0.01), which were consistent with the aforementioned results. Our study suggested that the abnormal elements in the serum of BTBR mice may cause oxidative stress and inflammation in prefrontal cortex, which might contribute to increase the understanding of ASD pathogenesis.
自闭症谱系障碍（ASD）是一种在幼儿期出现的神经发育障碍。然而，ASD发病机制背后的原因仍不清楚。本研究调查了BTBR T + tf/J（BTBR）小鼠血清和前额叶皮质中元素的变化及潜在机制。雄性BTBR小鼠作为实验组，C57BL/6 J（C57）小鼠作为对照组（n = 15）。在监测行为测试后，通过电感耦合等离子体质谱法（ICP-MS）分析小鼠的血清和前额叶皮质。结果表明，与C57小鼠相比，BTBR小鼠的铜（Cu）水平升高，而钙（Ca）、镁（Mg）、硒（Se）、钴（Co）、铁（Fe）和锌（Zn）水平降低（p < 0.01）。血清中上述差异元素的水平与前额叶皮质中的水平呈正相关。同时，前额叶皮质中的差异元素与BTBR小鼠的总行进距离（旷场试验）和埋珠数量（埋珠试验）相关（p < 0.05或p < 0.01）。血清中异常变化的元素可能穿过血脑屏障进入大脑，导致氧化应激，引发炎症。此外，BTBR小鼠前额叶皮质中包括肿瘤坏死因子-α（TNF-α）、核因子κB（NF-κB）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）在内的炎症相关指标水平升高（p < 0.01），这与上述结果一致。我们的研究表明，BTBR小鼠血清中的异常元素可能导致前额叶皮质中的氧化应激和炎症，这可能有助于加深对ASD发病机制的理解。
