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Title: Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure

Abstract

The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O3) exposure in aged mice, where increased blood brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C57BL/6 male mice, aged 8-10 weeks or 12–18 months were exposed to either filtered air (FA) or 1.0 ppm O3 for 4 hours; animals received a single IP injection of sodium fluorescein (FSCN) 20 hours post-exposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. β-amyloid protein expression was assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 hours post-O3 exposure. Flow cytometry analysis of brains revealed increased microglia “activation” and presentation of CD11b, F4/80 and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and β-amyloid protein expression after O3 insult. The aged cerebellum was particularly vulnerable to acute O3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C+ inflammatory monocytes after insult, which were not significantly increased in themore » young cerebellum. O3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Furthermore, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O3 exposure, leading to greater neuroinflammatory outcomes.« less

Authors:
 [1];  [2];  [3];  [3];  [3];  [3];  [2];  [2];  [3]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States)
  2. Univ. of New Mexico Health Sciences Center, Albuquerque, NM (United States)
  3. Univ. of New Mexico, Albuquerque, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE
OSTI Identifier:
1419764
Report Number(s):
LA-UR-18-20155
Journal ID: ISSN 1096-6080
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Toxicological Sciences
Additional Journal Information:
Journal Volume: 163; Journal Issue: 1; Journal ID: ISSN 1096-6080
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Biological Science; neuroinflammation; microglia; aging; reproductive & developmental toxicology; ozone; blood–brain barrier; inhalation toxicology; respiratory toxicology

Citation Formats

Tyler, Christina R., Noor, Shahani, Young, Tamara, Rivero, Valeria, Sanchez, Bethany, Lucas, Selita, Caldwell, Kevin K., Milligan, Erin D., and Campen, Matthew J. Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure. United States: N. p., 2018. Web. doi:10.1093/toxsci/kfy014.
Tyler, Christina R., Noor, Shahani, Young, Tamara, Rivero, Valeria, Sanchez, Bethany, Lucas, Selita, Caldwell, Kevin K., Milligan, Erin D., & Campen, Matthew J. Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure. United States. doi:10.1093/toxsci/kfy014.
Tyler, Christina R., Noor, Shahani, Young, Tamara, Rivero, Valeria, Sanchez, Bethany, Lucas, Selita, Caldwell, Kevin K., Milligan, Erin D., and Campen, Matthew J. Sat . "Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure". United States. doi:10.1093/toxsci/kfy014. https://www.osti.gov/servlets/purl/1419764.
@article{osti_1419764,
title = {Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure},
author = {Tyler, Christina R. and Noor, Shahani and Young, Tamara and Rivero, Valeria and Sanchez, Bethany and Lucas, Selita and Caldwell, Kevin K. and Milligan, Erin D. and Campen, Matthew J.},
abstractNote = {The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O3) exposure in aged mice, where increased blood brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C57BL/6 male mice, aged 8-10 weeks or 12–18 months were exposed to either filtered air (FA) or 1.0 ppm O3 for 4 hours; animals received a single IP injection of sodium fluorescein (FSCN) 20 hours post-exposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. β-amyloid protein expression was assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 hours post-O3 exposure. Flow cytometry analysis of brains revealed increased microglia “activation” and presentation of CD11b, F4/80 and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and β-amyloid protein expression after O3 insult. The aged cerebellum was particularly vulnerable to acute O3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C+ inflammatory monocytes after insult, which were not significantly increased in the young cerebellum. O3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Furthermore, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O3 exposure, leading to greater neuroinflammatory outcomes.},
doi = {10.1093/toxsci/kfy014},
journal = {Toxicological Sciences},
number = 1,
volume = 163,
place = {United States},
year = {2018},
month = {1}
}

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Figures / Tables:

Table 1 Table 1: Flow cytometry markers for immune cells of interest.

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