PDF(Pubmed)
Abstract：
Patients with asthma experience elevated rates of mental illness. However, the molecular links underlying such lung-brain crosstalk remain ambiguous. Hypothalamic dysfunction is observed in many psychiatric disorders, particularly those with an inflammatory component due to many hypothalamic regions being unprotected by the blood-brain barrier. To gain a better insight into such neuropsychiatric sequelae, this study investigated gene expression differences in the hypothalamus following lung inflammation (asthma) induction in mice, using RNA transcriptome profiling. BALB/c mice were challenged with either bacterial lipopolysaccharide (LPS, E. coli) or ovalbumin (OVA) allergens or saline control (n = 7 per group), and lung inflammation was confirmed via histological examination of postmortem lung tissue. The majority of the hypothalamus was micro-dissected, and total RNA was extracted for sequencing. Differential expression analysis identified 31 statistically significant single genes (false discovery rate FDR5%) altered in expression following LPS exposure compared to controls; however, none were significantly changed following OVA treatment, suggesting a milder hypothalamic response. When gene sets were examined, 48 were upregulated and 8 were downregulated in both asthma groups relative to controls. REACTOME enrichment analysis suggests these gene sets are involved in signal transduction metabolism, immune response and neuroplasticity. Interestingly, we identified five altered gene sets directly associated with neurotransmitter signaling. Intriguingly, many of these altered gene sets can influence mental health and or/neuroinflammation in humans. These findings help characterize the links between asthma-induced lung inflammation and the brain and may assist in identifying relevant pathways and therapeutic targets for future intervention.
摘要：
哮喘患者的精神疾病发生率升高。然而,这种肺脑串扰背后的分子联系仍然不明确。在许多精神疾病中观察到下丘脑功能障碍，特别是那些由于许多下丘脑区域未受到血脑屏障保护而具有炎症成分的患者。为了更好地了解这种神经精神后遗症，这项研究调查了小鼠肺部炎症（哮喘）诱导后下丘脑的基因表达差异，使用RNA转录组分析。BALB/c小鼠用细菌脂多糖(LPS，大肠杆菌）或卵清蛋白（OVA）过敏原或盐水对照（每组n=7），肺部炎症通过死后肺组织的组织学检查得到证实。下丘脑的大部分是显微解剖的，提取总RNA进行测序。差异表达分析确定了与对照组相比，暴露于LPS后表达发生改变的31个具有统计学意义的单基因（错误发现率FDR5%）；然而，OVA治疗后无明显变化，表明下丘脑有较温和的反应.当检查基因集时，相对于对照组，两个哮喘组48个上调，8个下调。REACTOME富集分析表明这些基因集参与信号转导代谢，免疫反应和神经可塑性。有趣的是,我们发现了5个与神经递质信号直接相关的基因改变.有趣的是，许多这些改变的基因集可以影响人类的心理健康和/或神经炎症。这些发现有助于表征哮喘诱导的肺部炎症与大脑之间的联系，并可能有助于确定相关途径和治疗目标，以便将来进行干预。
