青春期前后的哮喘症状会导致小鼠出现与成年焦虑相关的行为和神经生物学过程。

Peri-adolescent asthma symptoms cause adult anxiety-related behavior and neurobiological processes in mice.

作者信息

Caulfield Jasmine I, Caruso Michael J, Michael Kerry C, Bourne Rebecca A, Chirichella Nicole R, Klein Laura C, Craig Timothy, Bonneau Robert H, August Avery, Cavigelli Sonia A

机构信息

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.

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.

出版信息

Behav Brain Res. 2017 May 30;326:244-255. doi: 10.1016/j.bbr.2017.02.046. Epub 2017 Mar 8.

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.

摘要

人类和动物研究表明,青春期的身体挑战和应激源会对与内化障碍(如焦虑和抑郁)相关的行为和神经生物学发育产生重大影响。鉴于青春期哮喘的患病率以及哮喘患者内化障碍发生率的增加,我们使用小鼠模型来测试青少年过敏性哮喘的哪些症状(气道炎症或呼吸困难)会导致成年后与焦虑和抑郁相关的行为及脑功能改变。为了模拟年轻BALB/cJ小鼠(出生后第7 - 57天;N = 98)的过敏性哮喘症状,我们通过反复鼻内给予屋尘螨提取物(人类最常见的气传变应原)诱导肺部炎症,并通过雾化乙酰甲胆碱(非选择性毒蕈碱受体激动剂)诱导支气管收缩。除对照组外,三个实验组包括:(1)“仅气道炎症”,每周暴露于变应原3次;(2)“仅呼吸困难”,每周暴露于乙酰甲胆碱1次;(3)“气道炎症 + 呼吸困难”,暴露于变应原和乙酰甲胆碱。与对照组相比,青春期经历乙酰甲胆碱诱导的呼吸困难的小鼠在成年早期(P60)在高架十字迷宫开放臂上的停留时间减少了约20%,成年期(P75)脑干5-羟色胺转运体(SERT)mRNA表达减少了约30%,海马5-羟色胺受体1a(5Htr1a)和促肾上腺皮质激素释放激素受体1(Crhr1)表达增加了约50%。这是首个证据表明,实验诱导的青少年哮喘临床症状在哮喘干预完成数周后会改变成年后与焦虑相关的行为和脑功能。

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