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Inhalation of Air Particulate Matter Accelerates Neuroinflammation and Amyloid‐beta Accumulation in APP/PS1 Mice
Author(s) -
Mackos Amy,
Sahu Bijayani,
O’Piela Devin,
Combs Colin,
Wold Loren
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09330
Subject(s) - neuroinflammation , microglia , cd68 , genetically modified mouse , hippocampal formation , pathology , inhalation exposure , alzheimer's disease , chemistry , immunohistochemistry , medicine , endocrinology , transgene , inflammation , biochemistry , toxicity , disease , gene
Alzheimer disease (AD) which is a progressive, neurodegenerative disease characterized by neuroinflammation and accumulation of amyloid‐β (Aβ) fibers leading to neuronal death. It is theorized that a combination of host genetics and environmental factors contribute to AD development and progression, however the trigger for neuroinflammation and Aβ development has remained elusive. One such environmental exposure linked to AD development and progression is air pollution. Thus, we designed a study to test our hypothesis that air particulate matter exposure accelerates AD development and progression. Male, wild type (WT) C57Bl/6 and AD transgenic mice, APPswe/PSEN1dE9 (APP/PS1), were exposed to either filtered air (FA) or air particulate matter sized under 2.5 μm (PM 2.5 ) for 6 hrs/day, 5 days/week for 3 months. Brain tissue was collected at the end of the 3 month exposure and was either flash frozen or formalin‐fixed. Results demonstrated a significant increase in hippocampal Aβ accumulation in PM 2.5 ‐exposed APP/PS1 mice over that of FA‐exposed APP/PS1 animals. PM 2.5 ‐exposed WT mice did not develop Aβ plaques. Immune markers CD68 (tissue macrophage) and IBA1 (activated microglia) and the glial marker GFAP (activated astrocytes), as assessed by immunohistochemistry, were also significantly increased in PM 2.5 ‐exposed APP/PS1 mice over their FA‐exposed counterparts. PM 2.5 ‐exposure did not lead to enhanced levels of CD68, IBA1, or GFAP in WT mice. Taken together, these data suggest that airborne particulate matter has the propensity to alter the brain environment in mice genetically predisposed to develop Aβ in a way that mimics early AD‐like pathology. Support or Funding Information Funding support from AG057046 to LEW and CKC.