Activation of the Stress Axis and Neurochemical Alterations in Specific Brain Areas by Concentrated Ambient Particle Exposure with Concomitant Allergic Airway Disease

摘要

OBJECTIVE: Exposure to ambient paniculate matter (PM) has been linked to respiratory diseases in people living in urban communities.The mechanism by which PM produces these diseases is not clear.We hypothesized that PM could act on the brain directly to stimulate the stress axis and predispose individuals to these diseases.The purpose of this study was to test if exposure to PM can affect brain areas involved in the regulation of neuroendocrine functions,especially the stress axis,and to study whether the presence of preexisting allergic airway disease aggravates the stress response. DESIGN: Adult male rats (n = 8/group) with or without ovalbumin (OVA)-induced allergic airway disease were exposed to concentrated air particles containing PM with an aerodynamic diameter <= 2.5 mum (PM_(2.5)) for 8 hr,generated from ambient air in an urban Grand Rapids,Michigan,community using a mobile air research laboratory (AirCARE 1).Control animals were exposed to normal air and were treated with saline. MEASUREMENTS: A day after PM2.5 exposure,animals were sacrificed and the brains were removed,frozen,and sectioned.The paraventricular nucleus (PVN) and other brain nuclei were micro-dissected,and the concentrations of aminergic neurotransmitters and their metabolites were measured using high-performance liquid chromatography with electrochemical detection.Serum corticosterone levels were measured using radioimmunoassay. RESULTS: A significant increase in the concentration (mean +- SE,pg/mug protein) of norepinephrine in the PVN was produced by exposure to concentrated ambient particles (CAPs) or OVA alone (12.45 +- 2.7 and 15.84 +- 2.8,respectively) or after sensitization with OVA (19.06 +- 3.8) compared with controls (7.98 +- 1.3;p < 0.05).Serum corticosterone (mean +- SE,ng/mL) was significantly elevated in the OVA + CAPs group (242.786 +- 33.315) and in the OVA-presensitized group (242.786 +- 33.315) compared with CAP exposure alone (114.55 +- 20.9).Exposure to CAPs (alone or in combination with OVA pretreatment) can activate the stress axis,and this could probably play a role in aggravating allergic airway disease.