Peri-adolescent asthma symptoms cause adult anxiety-related behavior and neurobiological processes in mice.
Peri-adolescent asthma symptoms cause adult anxiety-related behavior and neurobiological processes in mice.
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DOI：
10.1016/j.bbr.2017.02.046
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发表时间：
2017-05-30
影响因子：
2.7
通讯作者：
Cavigelli SA
中科院分区：
文献类型：
--
作者：
Caulfield JI;Caruso MJ;Michael KC;Bourne RA;Chirichella NR;Klein LC;Craig T;Bonneau RH;August A;Cavigelli SA
人类和动物研究表明，青春期的身体挑战和压力源可能会对与焦虑和抑郁等内化性障碍相关的行为和神经生物学发展产生重大影响。鉴于哮喘在青春期的流行以及患有哮喘的人类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(呼吸道炎症或呼吸困难)是否以及哪些症状会导致成人焦虑和抑郁相关的行为和大脑功能。为了模拟幼年BALB/CJ小鼠过敏性哮喘的症状(出生后7-57天[P]7-57；N=98)，我们通过反复鼻腔给药屋尘螨提取物(人类最常见的空气过敏原)和雾化吸入乙酰甲胆碱(非选择性M受体激动剂)来诱导肺部炎症。除对照组外，还有3个试验组：(1)“仅呼吸道炎症”，每周暴露3次过敏原；(2)“仅呼吸困难”，每周暴露一次乙酰甲胆碱；(3)“呼吸道炎症+呼吸困难”，过敏原和乙酰甲胆碱暴露。与对照组相比，在青春期经历了乙酰甲胆碱诱导的劳累呼吸的小鼠在成年早期在高架迷宫张开双臂上的时间减少了约20%(P60)，脑干5-羟色胺转运体(SERT)mRNA的表达减少了约30%，成年后海马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)的表达增加了约50%(P75)。这是实验诱导的青少年哮喘临床症状在哮喘治疗完成几周后改变成人焦虑相关行为和大脑功能的第一个证据。
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.