TY - JOUR
T1 - Alpha2B-adrenergic receptor overexpression in the brain potentiate air pollution-induced behavior and blood pressure changes
AU - Rao, Xiaoquan
AU - Asico, Laureano D.
AU - Zanos, Panos
AU - Mahabeleshwar, Ganapati H.
AU - Gangwar, Roopesh Singh
AU - Xia, Chang
AU - Duan, Lihua
AU - Cisse, Yasmine Marie
AU - Rengasamy, Palanivel
AU - Jose, Pedro A.
AU - Gould, Todd D.
AU - Nelson, Randy
AU - Biswal, Shyam
AU - Chen, Lung Chi
AU - Zhong, Jixin
AU - Rajagopalan, Sanjay
N1 - Funding Information:
National Institute of Health (R01ES015146 and R01ES019616 to S.R., K99ES026241 to X.R., K01DK105108 to J.Z., HL126626 and HL141423 to G.H.M.) and American Heart Association (17GRNT33670485 to J.Z.).
Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Fine ambient particulate matter (PM2.5) is able to induce sympathetic activation and inflammation in the brain. However, direct evidence demonstrating an essential role of sympathetic activation in PM2.5-associated disease progression is lacking. We assess the contribution of a2B-adrenergic receptor (Adra2b) in air pollution-associated hypertension and behavioral changes in this study. Wild-type mice and Adra2b-transgenic mice overexpressing Adra2b in the brain (Adra2bTg) were exposed to concentrated PM2.5 or filtered air for 3 months via a versatile aerosol concentrator exposure system. Mice were fed with a high salt diet (4.0% NaCl) for 1 week at week 11 of exposure to induce blood pressure elevation. Intra-arterial blood pressure was monitored by radio-telemetry and behavior changes were assessed by open field, light-dark, and prepulse inhibition tests. PM2.5 exposure increased Adra2b in the brain of wild-type mice. Adra2b overexpression enhanced the anxiety-like behavior and high salt diet-induced blood pressure elevation in response to air pollution but not filtered air exposure. Adra2b overexpression induced upregulation of inflammatory genes such as TLR2, TLR4, and IL-6 in the brain exposed to PM2.5. In addition, there were increased frequencies of activated effector T cells and increased expression of oxidative stress-related genes, such as SOD1, NQO1, Nrf2, and Gclm in Adra2bTg mice compared with wild-type mice. Our results provide new evidence of distinct behavioral changes consistent with anxiety and blood pressure elevation in response to high salt intake and air pollution exposure, highlighting the importance of centrally expressed Adra2b in the vulnerability to air pollution exposure.
AB - Fine ambient particulate matter (PM2.5) is able to induce sympathetic activation and inflammation in the brain. However, direct evidence demonstrating an essential role of sympathetic activation in PM2.5-associated disease progression is lacking. We assess the contribution of a2B-adrenergic receptor (Adra2b) in air pollution-associated hypertension and behavioral changes in this study. Wild-type mice and Adra2b-transgenic mice overexpressing Adra2b in the brain (Adra2bTg) were exposed to concentrated PM2.5 or filtered air for 3 months via a versatile aerosol concentrator exposure system. Mice were fed with a high salt diet (4.0% NaCl) for 1 week at week 11 of exposure to induce blood pressure elevation. Intra-arterial blood pressure was monitored by radio-telemetry and behavior changes were assessed by open field, light-dark, and prepulse inhibition tests. PM2.5 exposure increased Adra2b in the brain of wild-type mice. Adra2b overexpression enhanced the anxiety-like behavior and high salt diet-induced blood pressure elevation in response to air pollution but not filtered air exposure. Adra2b overexpression induced upregulation of inflammatory genes such as TLR2, TLR4, and IL-6 in the brain exposed to PM2.5. In addition, there were increased frequencies of activated effector T cells and increased expression of oxidative stress-related genes, such as SOD1, NQO1, Nrf2, and Gclm in Adra2bTg mice compared with wild-type mice. Our results provide new evidence of distinct behavioral changes consistent with anxiety and blood pressure elevation in response to high salt intake and air pollution exposure, highlighting the importance of centrally expressed Adra2b in the vulnerability to air pollution exposure.
KW - Adrenergic receptor
KW - Air pollution
KW - Behavior
KW - Blood pressure
KW - Particulate matter
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U2 - 10.1093/toxsci/kfz025
DO - 10.1093/toxsci/kfz025
M3 - Article
C2 - 30812033
AN - SCOPUS:85065644590
SN - 1096-6080
VL - 169
SP - 95
EP - 107
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 1
ER -