title: Sensory neural responses to ozone exposure during early postnatal development in rat airways.
abstract: Airway infections or irritant exposures during early postnatal periods may contribute to the onset of childhood asthma. The purpose of this study was to examine critical periods of postnatal airway development during which ozone (O(3)) exposure leads to heightened neural responses. Rats were exposed to O(3) (2 ppm) or filtered air for 1 hour on specific postnatal days (PDs) between PD1 and PD29, and killed 24 hours after exposure. In a second experiment, rats were exposed to O(3) on PD2-PD6, inside a proposed critical period of development, or on PD19-PD23, outside the critical period. Both groups were re-exposed to O(3) on PD28, and killed 24 hours later. Airways were removed, fixed, and prepared for substance P (SP) immunocytochemistry. SP nerve fiber density (NFD) in control extrapulmonary (EXP) epithelium/lamina propria (EPLP) increased threefold, from 1% to 3.3% from PD1-PD3 through PD13-PD15, and maintained through PD29. Upon O(3) exposure, SP-NFD in EXP-smooth muscle (SM) and intrapulmonary (INT)-SM increased at least twofold at PD1-PD3 through PD13-PD15 in comparison to air exposure. No change was observed at PD21-PD22 or PD28-PD29. In critical period studies, SP-NFD in the INT-SM and EXP-SM of the PD2-PD6 O(3) group re-exposed to O(3) on PD28 was significantly higher than that of the group exposed at PD19-PD23 and re-exposed at PD28. These findings suggest that O(3)-mediated changes in sensory innervation of SM are more responsive during earlier postnatal development. Enhanced responsiveness of airway sensory nerves may be a contributing mechanism of increased susceptibility to environmental exposures observed in human infants and children.
authors.affiliation: Department of Neurobiology and Anatomy, West Virginia University, Morgantown, WV 26506, USA. dhunter@hsc.wvu.edu
authors.forename: Dawn D
authors.initials: DD
authors.lastname: Hunter
authors.forename: Zhongxin
authors.initials: Z
authors.lastname: Wu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Dey
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000254:growth & development* / Q000294:innervation*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D010126:Ozone / Q000494:pharmacology*; D051381:Rats; D012129:Respiratory Function Tests; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D013997:Time Factors
chemical_list: D013373:Substance P; D010126:Ozone