Perivascular Accumulation of β-Sheet-Rich Proteins in Offspring Brain following Maternal Exposure to Carbon Black Nanoparticles.
Perivascular Accumulation of β-Sheet-Rich Proteins in Offspring Brain following Maternal Exposure to Carbon Black Nanoparticles.
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DOI：
10.3389/fncel.2017.00092
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发表时间：
2017
影响因子：
5.3
通讯作者：
Umezawa M
中科院分区：
文献类型：
--
作者：
Onoda A;Kawasaki T;Tsukiyama K;Takeda K;Umezawa M
大脑发育过程中的环境刺激是神经退行性疾病发展的重要危险因素。临床证据表明，产前暴露于颗粒空气污染物会导致发育中的大脑神经血管单位的弥漫性损伤，并加速神经退行性变。母体暴露于炭黑纳米颗粒（CB-NPs），用作颗粒空气污染的模型，诱导持久的弥漫性血管周围异常。我们的目的是全面表征血管周围的异常与母体NPs暴露使用傅立叶变换红外显微光谱（原位FT-IR）和经典的染色分析。在妊娠第5天和第9天，用CB-NP悬浮液（每次95 μg/kg）鼻内处理妊娠ICR小鼠。在出生后6周收集脑并切片以制备10 μ m厚的连续切片。原位FT-IR的反射光谱使用围绕中心血管的晶格测量（x轴：7，y轴：7，30 μm孔径）获得。我们还进行了蛋白质二级结构的作图分析。连续切片用过碘酸-希夫或免疫荧光染色以检查血管周围区域的表型。从血管周围地区的光谱中的酰胺I带的峰被移动的母体NP曝光。然而，在暴露组的一只小鼠中存在两种类型的峰移。一些船舶有一个大的峰移和其他人有一个小的峰移。原位红外光谱结合传统染色显示，高表达胶质细胞酸性蛋白和水通道蛋白4的星形胶质细胞和溶酶体颗粒增大的血管周围巨噬细胞（PVM）的荧光峰明显偏移。此外，蛋白质二级结构分析表明，母体NPs暴露导致大多数接近显示组织病理学变化的中心血管的区域中β-折叠含量增加和α-螺旋含量减少。这些结果表明，通过母体NP暴露变性的富含β-片层的废物蛋白可能在血管周围空间中积累，因为它们被大脑中的清除系统处理。这可能反过来导致PVM变性和星形胶质细胞活化。在大脑发育期间，富含β-片层的废物蛋白质在血管周围积聚后，暴露于颗粒空气污染物可能会增加神经变性的风险。
Environmental stimulation during brain development is an important risk factor for the development of neurodegenerative disease. Clinical evidence indicates that prenatal exposure to particulate air pollutants leads to diffuse damage to the neurovascular unit in the developing brain and accelerates neurodegeneration. Maternal exposure to carbon black nanoparticles (CB-NPs), used as a model for particulate air pollution, induces long-lasting diffuse perivascular abnormalities. We aimed to comprehensively characterize the perivascular abnormalities related to maternal NPs exposure using Fourier transform infrared microspectroscopy (in situ FT-IR) and classical staining analysis. Pregnant ICR mice were intranasally treated with a CB-NPs suspension (95 μg/kg at a time) on gestational days 5 and 9. Brains were collected 6 weeks after birth and sliced to prepare 10-μm-thick serial sections. Reflective spectra of in situ FT-IR were acquired using lattice measurements (x-axis: 7, y-axis: 7, 30-μm apertures) around a centered blood vessel. We also performed mapping analysis of protein secondary structures. Serial sections were stained with using periodic acid-Schiff or immunofluorescence to examine the phenotypes of the perivascular areas. Peaks of amide I bands in spectra from perivascular areas were shifted by maternal NPs exposure. However, there were two types of peak-shift in one mouse in the exposure group. Some vessels had a large peak-shift and others had a small peak-shift. In situ FT-IR combined with traditional staining revealed that the large peak-shift was induced around blood vessel adjacent to astrocytes with glial fibrillary acidic protein and aquaporin-4 over-expression and perivascular macrophages (PVMs) with enlarged lysosome granules. Furthermore, protein secondary structural analysis indicated that maternal NPs exposure led to increases in β-sheet content and decreases in α-helix content in areas that are mostly close to the centered blood vessel displaying histopathological changes. These results suggest that β-sheet-rich waste proteins, which are denatured by maternal NPs exposure, likely accumulate in the perivascular space as they are processed by the clearance systems in the brain. This may in turn lead the denaturation of PVMs and astrocyte activation. The risk of neurodegeneration may be enhanced by exposure to particulate air pollutants during brain development following the perivascular accumulation of β-sheet-rich waste proteins.