Inhaled corticosteroids as treatment for adolescent asthma: effects on adult anxiety-related outcomes in a murine model.
Inhaled corticosteroids as treatment for adolescent asthma: effects on adult anxiety-related outcomes in a murine model.
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DOI：
10.1007/s00213-020-05666-x
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发表时间：
2021-01
影响因子：
3.4
通讯作者：
Cavigelli SA
中科院分区：
文献类型：
--
作者：
Caulfield JI;Ching AM;Cover EM;August A;Craig T;Kamens HM;Cavigelli SA
过敏性哮喘，通常用吸入性皮质类固醇（ICS）控制，是18岁以下青少年的主要慢性健康状况。在这段青春期前后，大脑会发生显著的成熟。先前的研究表明，慢性炎症和皮质类固醇药物都会增加患焦虑等内化障碍的风险。为了确定慢性ICS治疗是否加重或减轻与发育性过敏性哮喘相关的焦虑症状，我们使用小鼠模型来分离ICS（丙酸氟替卡松，FLU）与气道炎症（用屋尘螨提取物诱导，HDM）的影响。在发育期间，雄性和雌性BALB/cJ小鼠重复暴露于HDM或生理盐水加四种FLU剂量（无/溶剂、低、中或高）之一。在成年期，我们评估了肺部炎症、循环和分泌的皮质类固醇、焦虑样行为以及压力和情绪调节大脑区域的基因表达。FLU治疗降低了体重和焦虑样行为，增加了粪便皮质酮代谢物浓度和腹侧海马中Crhr 2基因表达。仅在盐水/非HDM暴露小鼠中观察到FLU效应，并且所用FLU剂量未显著降低HDM诱导的气道炎症。与男性相比，女性的血清和粪便中皮质酮浓度更高，焦虑样行为更少，腹侧海马和前额叶皮质中Crhr 1基因表达更低。这些研究结果表明，用于过敏性哮喘青少年的类固醇药物可能不会加剧焦虑相关症状，并且应该避免在没有健康状况的儿童/青少年中使用。研究结果为今后在儿童或青少年发育期间使用皮质类固醇药物提供了信息。
Allergic asthma, typically controlled with inhaled corticosteroids (ICS), is the leading chronic health condition for youth under 18 years of age. During this peri-adolescent period, significant brain maturation occurs. Prior studies indicate that both chronic inflammation and corticosteroid medications increase risk for developing an internalizing disorder like anxiety. To determine if chronic ICS treatments exacerbate or alleviate anxiety symptoms associated with developmental allergic asthma, we used a mouse model to isolate the influence of ICS (fluticasone propionate, FLU) vs. airway inflammation (induced with house dust mite extract, HDM). During development, male and female BALB/cJ mice were repeatedly exposed to HDM or saline plus one of four FLU doses (none/vehicle, low, moderate, or high). In adulthood, we assessed lung inflammation, circulating and excreted corticosteroids, anxiety-like behavior, and gene expression in stress and emotion regulation brain regions. FLU treatment decreased body weight and anxiety-like behavior and increased fecal corticosterone metabolite concentrations and Crhr2 gene expression in ventral hippocampus. FLU effects were only observed in saline/non-HDM-exposed mice, and the FLU doses used did not significantly decrease HDM-induced airway inflammation. Females had greater serum and fecal corticosterone concentrations, less anxiety-like behavior, and lower Crhr1 gene expression in ventral hippocampus and prefrontal cortex than males. These findings suggest that steroid medications for youth with allergic asthma may not exacerbate anxiety-related symptoms and should be avoided in children/adolescents without a health condition. The results are informative to future work on the use of corticosteroid medications during childhood or adolescent development.
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影响因子：
4.4
作者：
De Leonibus, Chiara;Attanasi, Marina;Mohn, Angelika
通讯作者：
Mohn, Angelika
影响因子：
2.7
作者：
Caulfield JI;Caruso MJ;Michael KC;Bourne RA;Chirichella NR;Klein LC;Craig T;Bonneau RH;August A;Cavigelli SA
通讯作者：
Cavigelli SA
影响因子：
11
作者：
通讯作者：
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影响因子：
2.7
作者：
File, SE
通讯作者：
File, SE
影响因子：
6.1
作者：
De Graaf-In't Veld, C.;Garrelds, I. M.;Gerth Van Wijk, R.
通讯作者：
Gerth Van Wijk, R.