Alpha2B-Adrenergic Receptor Overexpression in the Brain Potentiate Air Pollution-induced Behavior and Blood Pressure Changes

Xiaoquan Rao, Laureano D. Asico, Panos Zanos, Ganapati H. Mahabeleshwar, Roopesh Singh Gangwar, Chang Xia, Lihua Duan, Yasmine Marie Cisse, Palanivel Rengasamy, Pedro A. Jose, Todd D. Gould, Randy Nelson, Shyam Biswal, Lung Chi Chen, Jixin Zhong, Sanjay Rajagopalan

Research output: Contribution to journalArticle

Abstract

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 α2B-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.

Original languageEnglish (US)
Pages (from-to)95-107
Number of pages13
JournalToxicological sciences : an official journal of the Society of Toxicology
Volume169
Issue number1
DOIs
StatePublished - May 1 2019

Fingerprint

Blood pressure
Air Pollution
Air pollution
Adrenergic Receptors
Brain
Blood Pressure
Salts
Nutrition
Genes
Chemical activation
Anxiety
Oxidative stress
Air
T-cells
Particulate Matter
Diet
Telemetering
Aerosols
Telemetry
Encephalitis

Keywords

  • adrenergic receptor
  • air pollution
  • behavior
  • blood pressure
  • particulate matter

ASJC Scopus subject areas

  • Toxicology

Cite this

Alpha2B-Adrenergic Receptor Overexpression in the Brain Potentiate Air Pollution-induced Behavior and Blood Pressure Changes. / Rao, Xiaoquan; Asico, Laureano D.; Zanos, Panos; Mahabeleshwar, Ganapati H.; Singh Gangwar, Roopesh; Xia, Chang; Duan, Lihua; Cisse, Yasmine Marie; Rengasamy, Palanivel; Jose, Pedro A.; Gould, Todd D.; Nelson, Randy; Biswal, Shyam; Chen, Lung Chi; Zhong, Jixin; Rajagopalan, Sanjay.

In: Toxicological sciences : an official journal of the Society of Toxicology, Vol. 169, No. 1, 01.05.2019, p. 95-107.

Research output: Contribution to journalArticle

Rao, X, Asico, LD, Zanos, P, Mahabeleshwar, GH, Singh Gangwar, R, Xia, C, Duan, L, Cisse, YM, Rengasamy, P, Jose, PA, Gould, TD, Nelson, R, Biswal, S, Chen, LC, Zhong, J & Rajagopalan, S 2019, 'Alpha2B-Adrenergic Receptor Overexpression in the Brain Potentiate Air Pollution-induced Behavior and Blood Pressure Changes', Toxicological sciences : an official journal of the Society of Toxicology, vol. 169, no. 1, pp. 95-107. https://doi.org/10.1093/toxsci/kfz025
Rao, Xiaoquan ; Asico, Laureano D. ; Zanos, Panos ; Mahabeleshwar, Ganapati H. ; Singh Gangwar, Roopesh ; Xia, Chang ; Duan, Lihua ; Cisse, Yasmine Marie ; Rengasamy, Palanivel ; Jose, Pedro A. ; Gould, Todd D. ; Nelson, Randy ; Biswal, Shyam ; Chen, Lung Chi ; Zhong, Jixin ; Rajagopalan, Sanjay. / Alpha2B-Adrenergic Receptor Overexpression in the Brain Potentiate Air Pollution-induced Behavior and Blood Pressure Changes. In: Toxicological sciences : an official journal of the Society of Toxicology. 2019 ; Vol. 169, No. 1. pp. 95-107.
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