Wadsworth Center, New York State Department of Health, Center for Medical Science, 150 New Scotland Avenue, Albany, NY, 12208, USA.
University at Albany School of Public Health, Rensselaer, NY, USA.
Cell Stress Chaperones. 2023 Mar;28(2):201-217. doi: 10.1007/s12192-023-01331-2. Epub 2023 Feb 16.
Oxidative stress including decreased antioxidant enzyme activities, elevated lipid peroxidation, and accumulation of advanced glycation end products in the blood from children with autism spectrum disorders (ASD) has been reported. The mechanisms affecting the development of ASD remain unclear; however, toxic environmental exposures leading to oxidative stress have been proposed to play a significant role. The BTBRTItpr3/J (BTBR) strain provides a model to investigate the markers of oxidation in a mouse strain exhibiting ASD-like behavioral phenotypes. In the present study, we investigated the level of oxidative stress and its effects on immune cell populations, specifically oxidative stress affecting surface thiols (R-SH), intracellular glutathione (iGSH), and expression of brain biomarkers that may contribute to the development of the ASD-like phenotypes that have been observed and reported in BTBR mice. Lower levels of cell surface R-SH were detected on multiple immune cell subpopulations from blood, spleens, and lymph nodes and for sera R-SH levels of BTBR mice compared to C57BL/6 J (B6) mice. The iGSH levels of immune cell populations were also lower in the BTBR mice. Elevated protein expression of GATA3, TGM2, AhR, EPHX2, TSLP, PTEN, IRE1α, GDF15, and metallothionein in BTBR mice is supportive of an increased level of oxidative stress in BTBR mice and may underpin the pro-inflammatory immune state that has been reported in the BTBR strain. Results of a decreased antioxidant system suggest an important oxidative stress role in the development of the BTBR ASD-like phenotype.
已有报道称，自闭症谱系障碍（ASD）儿童的血液中存在氧化应激，包括抗氧化酶活性降低、脂质过氧化升高和晚期糖基化终产物积累。影响 ASD 发展的机制尚不清楚；然而，据提议，有毒的环境暴露导致氧化应激可能发挥重要作用。BTBRTItpr3/J（BTBR）品系提供了一个模型，用于研究表现出 ASD 样行为表型的小鼠品系中的氧化标志物。在本研究中，我们研究了氧化应激的水平及其对免疫细胞群体的影响，特别是影响表面硫醇（R-SH）、细胞内谷胱甘肽（iGSH）和脑生物标志物表达的氧化应激，这些生物标志物可能有助于解释在 BTBR 小鼠中观察到并报道的 ASD 样表型的发展。与 C57BL/6J（B6）小鼠相比，来自血液、脾脏和淋巴结的多个免疫细胞亚群以及 BTBR 小鼠的血清 R-SH 水平检测到细胞表面 R-SH 水平降低。BTBR 小鼠的免疫细胞群体的 iGSH 水平也较低。BTBR 小鼠中 GATA3、TGM2、AhR、EPHX2、TSLP、PTEN、IRE1α、GDF15 和金属硫蛋白的蛋白表达升高，支持 BTBR 小鼠中氧化应激水平升高，并可能构成 BTBR 品系中报道的促炎免疫状态的基础。抗氧化系统减少的结果表明，在 BTBR ASD 样表型的发展中，氧化应激起着重要作用。
