Abstract
Nano-particulate air pollution threatens developing brains and is epidemiologically related to neurodegenerative diseases involving deposition of misfolded proteins. However, the mechanism underlying developmental neurotoxicity by nanoparticles remains unknown. Here, we report that maternal exposure to low doses of carbon black nanoparticle (CB-NP) induces endoplasmic reticulum (ER) stress associated with accumulation of misfolded proteins. Notably, offspring specifically showed high induction of ER stress in perivascular macrophages and reactive astrocytes only around brain blood vessels, along with accumulation of β-sheet-rich proteins regarded as misfolded proteins. Our results suggest that maternal CB-NP exposure induced ER stress in PVMs and reactive astrocytes around blood vessels in the brain of offspring in mice. The induction of ER stress accompanied by the perivascular accumulation of misfolded proteins is likely to be associated with perivascular abnormalities and neurodegeneration, and development of neurodegenerative diseases related to particulate air pollution.
Highlights
Nano-particulate air pollution threatens developing brains and is epidemiologically related to neurodegenerative diseases involving deposition of misfolded proteins
To evaluate the expression of the endoplasmic reticulum (ER) stress markers in the reactive astrocytes highly expressing glial fibrillary acidic protein (GFAP), the marker proteins were visualized by double-immunofluorescence with GFAP
The number of activating transcription factor 6 (ATF6)-positive astrocytes, ATF6-positive perivascular macrophages (PVMs), and CHOP-positive PVMs was significantly increased after maternal exposure to low doses of carbon black nanoparticle (CB-NP) (Fig. 2A)
Summary
Nano-particulate air pollution threatens developing brains and is epidemiologically related to neurodegenerative diseases involving deposition of misfolded proteins. Epidemiological evidence suggests that exposure to particulate air pollution including nanoparticles is likely to increase risk for onset of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s diseases, later in life of offspring[5,6,7] Proteopathies, such as neurodegenerative diseases, are a class of conformational diseases that generally display deposition of misfolded proteins consisting of multiple β-sheet structures. The purpose of the current study is to investigate the ER stress along with accumulation of misfolded proteins and relationship between the ER stress and perivascular abnormalities in the brain of offspring mice maternally exposed to CB-NP
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