Perivascular Accumulation of β-Sheet-Rich Proteins in Offspring Brain following Maternal Exposure to Carbon Black Nanoparticles

Abstract

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.

Changes in the Secondary Structure and Assembly of Proteins on Fluoride Ceramic (CeF3) Nanoparticle Surfaces

“… 37 Thus, it is commonly used for the secondary structure analysis 38 that can also be applied to in situ analyses under microscopy. 39 Not only the secondary structure but also the aggregation of the Aβ peptide in solvents can be analyzed using FT-IR spectroscopy. 40 Hydrochloric acid (1 mmol/L) was used to maintain the dispersibility of the CeF 3 NPs.…”

The pathogenic effects of particulate matter on neurodegeneration: a review

“…The effects of PM on ER stress may contribute to the abnormal deposition of Aβ and α-synuclein in the brains of children from MCMA, leading to the susceptibility of late-life AD and onset of PD [ 15 ]. By using in situ Fourier transform infrared microspectroscopy to study the conformation of the proteins in the brain, proteins with β-sheet structure, a form of misfolded protein that are commonly seen in neurodegenerative diseases such as AD, accumulate in the perivascular space in the brains of the offsprings that were maternally exposed to carbon black nanoparticles [ 109 ]. These misfolded proteins may be in the process of clearance from the brain [ 109 ], which may activate the microglia and astrocytes.…”

“…By using in situ Fourier transform infrared microspectroscopy to study the conformation of the proteins in the brain, proteins with β-sheet structure, a form of misfolded protein that are commonly seen in neurodegenerative diseases such as AD, accumulate in the perivascular space in the brains of the offsprings that were maternally exposed to carbon black nanoparticles [ 109 ]. These misfolded proteins may be in the process of clearance from the brain [ 109 ], which may activate the microglia and astrocytes. Further analysis showed that perivascular macrophages and astrocytes were activated and showed ER stress in the offsprings’ brains when they were maternally exposed to carbon black nanoparticle [ 110 ].…”

Common Fatal Neurodegenerative Diseases Revisited: Beyond Age, Comorbidities, and Devastating Terminal Neuropathology There Is Hope With Prevention

“…The problem of NPs crossing the placental barrier at the early stages of fetal development, and the documentation of neurons and primitive glia displaying nuclear, organelle, and cytoplasmic Fe, Ti, and Al alloys, Hg, Cu, Ca, Sn, and Si NPs is a serious medical concern ( 15 ). Documentation of NPs in experimental animals shows maternal exposures resulting in severe offspring alterations in neurogenesis and synaptogenesis, perivascular accumulation of β sheet rich proteins, and perivascular ER stress with the accumulation of misfolded proteins in the developing brain ( 39 – 41 ).…”