Huck Institute for Life Sciences, Pennsylvania State University, 101 Life Sciences Building, University Park, PA, USA.
Department of Biobehavioral Health, Pennsylvania State University, 219 Biobehavioral Health Building, University Park, PA, USA.
Psychopharmacology (Berl). 2021 Jan;238(1):165-179. doi: 10.1007/s00213-020-05666-x. Epub 2020 Oct 4.
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 that they 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.
过敏性哮喘，通常通过吸入皮质类固醇（ICS）控制，是 18 岁以下青少年的主要慢性健康问题。在此青春期前期间，大脑会发生显著成熟。先前的研究表明，慢性炎症和皮质类固醇药物都会增加焦虑等内化障碍的风险。
为了确定慢性 ICS 治疗是否会加重或缓解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，HDM 诱导）的影响。
在发育过程中，雄性和雌性 BALB/cJ 小鼠反复暴露于 HDM 或盐水加四种 FLU 剂量（无/载体、低、中或高）之一。在成年期，我们评估了肺部炎症、循环和排泄皮质激素、焦虑样行为以及应激和情绪调节脑区的基因表达。
FLU 治疗降低了体重和焦虑样行为，并增加了粪便皮质酮代谢物浓度和腹侧海马中的 Crhr2 基因表达。FLU 作用仅在盐水/非 HDM 暴露的小鼠中观察到，并且所用的 FLU 剂量并未显著降低 HDM 诱导的气道炎症。雌性的血清和粪便皮质酮浓度高于雄性，焦虑样行为较少，腹侧海马和前额叶皮质中的 Crhr1 基因表达较低。
这些发现表明，用于过敏性哮喘的青少年的类固醇药物可能不会加重与焦虑相关的症状，并且在没有健康状况的儿童/青少年中应避免使用。这些结果为未来在儿童或青少年发育期间使用皮质类固醇药物的工作提供了信息。
