title: Peri-adolescent asthma symptoms cause adult anxiety-related behavior and neurobiological processes in mice.
abstract: Human and animal studies have shown that physical challenges and stressors during adolescence can have significant influences on behavioral and neurobiological development associated with internalizing disorders such as anxiety and depression. Given the prevalence of asthma during adolescence and increased rates of internalizing disorders in humans with asthma, we used a mouse model to test if and which symptoms of adolescent allergic asthma (airway inflammation or labored breathing) cause adult anxiety- and depression-related behavior and brain function. To mimic symptoms of allergic asthma in young BALB/cJ mice (postnatal days [P] 7-57; N=98), we induced lung inflammation with repeated intranasal administration of house dust mite extract (most common aeroallergen for humans) and bronchoconstriction with aerosolized methacholine (non-selective muscarinic receptor agonist). Three experimental groups, in addition to a control group, included: (1) "Airway inflammation only", allergen exposure 3 times/week, (2) "Labored breathing only", methacholine exposure once/week, and (3) "Airway inflammation+Labored breathing", allergen and methacholine exposure. Compared to controls, mice that experienced methacholine-induced labored breathing during adolescence displayed a ∼20% decrease in time on open arms of the elevated plus maze in early adulthood (P60), a ∼30% decrease in brainstem serotonin transporter (SERT) mRNA expression and a ∼50% increase in hippocampal serotonin receptor 1a (5Htr1a) and corticotropin releasing hormone receptor 1 (Crhr1) expression in adulthood (P75). This is the first evidence that experimentally-induced clinical symptoms of adolescent asthma alter adult anxiety-related behavior and brain function several weeks after completion of asthma manipulations.
authors.affiliation: Pennsylvania State University, Department of Biobehavioral Health, 219 Biobehavioral Health Building, University Park, PA 16802, USA; Pennsylvania State University, Huck Institute for Life Sciences, 101 Life Sciences Building, University Park, PA 16802, USA; Pennsylvania State University, Center for Brain, Behavior, and Cognition, University Park, PA 16802, USA. Electronic address: joc5376@psu.edu.
authors.forename: Jasmine I
authors.initials: JI
authors.lastname: Caulfield
authors.affiliation: Pennsylvania State University, Department of Biobehavioral Health, 219 Biobehavioral Health Building, University Park, PA 16802, USA; Pennsylvania State University, Center for Brain, Behavior, and Cognition, University Park, PA 16802, USA. Electronic address: mjc5038@psu.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caruso
authors.affiliation: Pennsylvania State University, Department of Biobehavioral Health, 219 Biobehavioral Health Building, University Park, PA 16802, USA. Electronic address: kmichael@morris.umn.edu.
authors.forename: Kerry C
authors.initials: KC
authors.lastname: Michael
authors.affiliation: Pennsylvania State University, Department of Biobehavioral Health, 219 Biobehavioral Health Building, University Park, PA 16802, USA. Electronic address: rac5105@psu.edu.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Bourne
authors.affiliation: Pennsylvania State University, Department of Biobehavioral Health, 219 Biobehavioral Health Building, University Park, PA 16802, USA. Electronic address: nrc5113@psu.edu.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Chirichella
authors.affiliation: Pennsylvania State University, Department of Biobehavioral Health, 219 Biobehavioral Health Building, University Park, PA 16802, USA. Electronic address: lxk18@psu.edu.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Klein
authors.affiliation: Penn State Hershey, Departments of Medicine and Pediatrics, Allergy, Asthma & Immunology Section, Hershey, PA 17033, USA. Electronic address: tcraig@hmc.psu.edu.
authors.forename: Timothy
authors.initials: T
authors.lastname: Craig
authors.affiliation: Pennsylvania State University College of Medicine, Departments of Microbiology and Immunology, and Pediatrics, 500 University Drive, Hershey, PA 17033, USA. Electronic address: rbonneau@psu.edu.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bonneau
authors.affiliation: Cornell University, Department of Microbiology and Immunology, C5 171 Veterinary Medical Center, Ithaca, NY 14853, USA. Electronic address: averyaugust@cornell.edu.
authors.forename: Avery
authors.initials: A
authors.lastname: August
authors.affiliation: Pennsylvania State University, Department of Biobehavioral Health, 219 Biobehavioral Health Building, University Park, PA 16802, USA; Pennsylvania State University, Huck Institute for Life Sciences, 101 Life Sciences Building, University Park, PA 16802, USA; Pennsylvania State University, Center for Brain, Behavior, and Cognition, University Park, PA 16802, USA. Electronic address: sac34@psu.edu.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Cavigelli
mesh_terms: D000367:Age Factors; D000818:Animals; D001007:Anxiety / Q000209:etiology*; D001249:Asthma / Q000139:chemically induced / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018721:Muscarinic Agonists / Q000494:pharmacology*; D039981:Pyroglyphidae / Q000276:immunology*; D012737:Sex Factors
chemical_list: D018721:Muscarinic Agonists; D016210:Methacholine Chloride
keywords: Adolescence; Anxiety; Asthma; House dust mite; Methacholine; Sex differences