Kachel Maria, Dola Antonina, Kubiak Mikołaj, Majewska Wiktoria, Nowakowska Joanna, Langwiński Wojciech, Hryhorowicz Szymon, Szczepankiewicz Aleksandra
Molecular and Cell Biology Unit, Poznan University of Medical Sciences, Poznan, Poland.
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
J Mol Neurosci. 2024 Dec 15;74(4):116. doi: 10.1007/s12031-024-02298-0.
Depression is a common disease that affects 3.8% of the global population. Despite various antidepressant treatments, one-third of patients do not respond to antidepressants, therefore augmentation with mood stabilizers such as lithium may be required in this group. One of the suggested pathomechanisms of depression is the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and recent reports showed that microRNAs (miRNA) can impact its activity by epigenetic regulation. We aimed to explore the miRNA expression profile in the depression model and its changes upon short-term and chronic lithium treatment in the rat brain (pituitary, hypothalamus, and hippocampus). We used a chronic mild stress rat model of depression and short- and long-term lithium treatment. The behavior was assessed by an open-field test. The miRNA expression profile in the pituitary was estimated by sequencing and validated in the hypothalamus and hippocampus with qPCR. We found several miRNAs in the pituitary that were significantly altered between CMS-exposed and control rats as well as after short- and long-term lithium treatment. MicroRNAs chosen for validation in the hypothalamus and hippocampus (rno-miR-146a-5p, rno-miR-127-3p) showed no significant changes in expression. We performed in silico analysis and estimated potential pathways involved in lithium action for miRNAs differentially expressed in the pituitary at different time points. Specific microRNA subsets showed altered expression in the pituitary in depression model upon short- and long-term lithium treatment. We identified that biological pathways of target genes for these altered miRNAs differ, with the Foxo pathway potentially involved in disease development.
抑郁症是一种常见疾病，影响着全球3.8%的人口。尽管有各种抗抑郁治疗方法，但仍有三分之一的患者对抗抑郁药无反应，因此这组患者可能需要使用锂盐等心境稳定剂进行增效治疗。抑郁症的一种假定发病机制是下丘脑-垂体-肾上腺（HPA）轴失调，最近的报告显示，微小RNA（miRNA）可通过表观遗传调控影响其活性。我们旨在探索抑郁症模型中的miRNA表达谱，以及大鼠脑（垂体、下丘脑和海马体）在短期和长期锂治疗后的变化。我们使用了抑郁症的慢性轻度应激大鼠模型以及短期和长期锂治疗。通过旷场试验评估行为。通过测序估计垂体中的miRNA表达谱，并在下丘脑和海马体中用qPCR进行验证。我们发现垂体中有几种miRNA在暴露于慢性轻度应激的大鼠与对照大鼠之间以及短期和长期锂治疗后有显著变化。选择在下丘脑和海马体中进行验证的miRNA（rno-miR-146a-5p、rno-miR-127-3p）表达无显著变化。我们进行了计算机分析，并估计了在不同时间点垂体中差异表达的miRNA参与锂作用的潜在途径。特定的miRNA亚群在抑郁症模型的垂体中，经短期和长期锂治疗后表达发生改变。我们发现这些改变的miRNA的靶基因的生物学途径不同，Foxo途径可能参与疾病发展。
