Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil.
Department of Neurosurgery, Friedrich-Alexander University, 91054 Erlangen, Germany.
Int J Mol Sci. 2021 Oct 6;22(19):10823. doi: 10.3390/ijms221910823.
(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-β processing in one-year-old transgenic (tg) mice with 12 copies of the murine S100B gene with specific consideration of sex and specific brain regions. (2) Methods: S100B and amyloid-β 42 (Aβ42) were quantified in serum, cerebrospinal fluid (CSF), adipose tissue, and different brain regions by ELISA in wild-type (wt) and S100Btg mice (each = 7 per group). Thioflavin T (ThT) and Aβ immunostaining were performed for visualization of Aβ deposition. (3) Results: S100B in serum, CSF, and brain was significantly increased in S100Btg mice of both sexes. Aβ42 was significantly increased in the hippocampus of male S100Btg mice ( = 0.0075), and the frontal cortex of female S100Btg mice ( = 0.0262). ThT and Aβ immunostaining demonstrated Aβ deposition in different brain regions in S100Btg mice of both sexes and female wt. (4) Conclusion: Our data validate this experimental model for studying the role of S100B in neurodegeneration and indicate that Aβ processing is sex-dependent and brain region-specific, which deserves further investigation of signaling pathways and behavioral responses.
（1）背景：钙结合蛋白 S100B 参与神经再生，但也与神经退行性变有关。这些相反的影响可能是由于暴露的浓度或持续时间造成的。我们研究了在具有 12 个鼠 S100B 基因拷贝的 1 岁转基因（tg）小鼠中，长期增加 S100B 水平对淀粉样蛋白-β（Aβ）加工的影响，并特别考虑了性别和特定脑区。（2）方法：通过 ELISA 在野生型（wt）和 S100Btg 小鼠（每组 = 7）的血清、脑脊液（CSF）、脂肪组织和不同脑区中定量 S100B 和 Aβ42（Aβ42）。通过 Thioflavin T（ThT）和 Aβ免疫染色来可视化 Aβ沉积。（3）结果：S100Btg 小鼠的血清、CSF 和脑内 S100B 均显著增加。雄性 S100Btg 小鼠的海马体（ = 0.0075）和雌性 S100Btg 小鼠的额皮质（ = 0.0262）中 Aβ42 显著增加。ThT 和 Aβ免疫染色显示 S100Btg 小鼠的不同脑区和雌性 wt 存在 Aβ沉积。（4）结论：我们的数据验证了这种实验模型在研究 S100B 在神经退行性变中的作用，并表明 Aβ加工具有性别依赖性和脑区特异性，值得进一步研究信号通路和行为反应。
