Laboratory of Neuroscience, Department of Biology, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi 274-8510, Japan.
Department of Functional Morphology, Shonan University of Medical Sciences, 16-48 Kamishinano, Totsuka-ku, Yokohama 244-0806, Japan.
Int J Mol Sci. 2023 Feb 5;24(4):3153. doi: 10.3390/ijms24043153.
It is difficult to evaluate the pre-symptomatic state of mental disorders and prevent its onset. Since stress could be a trigger of mental disorders, it may be helpful to identify stress-responsive biomarkers (stress markers) for the evaluation of stress levels. We have so far performed omics analyses of the rat brain and peripheral blood after various kinds of stress and have found numerous factors that respond to stress. In this study, we investigated the effects of relatively moderate stress on these factors in the rat to identify stress marker candidates. Adult male Wistar rats underwent water immersion stress for 12 h, 24 h, or 48 h. Stress caused weight loss and elevated serum corticosterone levels, and alterations regarded as anxiety and/or fear-like behaviors. Reverse-transcription PCR and Western blot analyses revealed significant alterations in the expressions of hippocampal genes and proteins by the stress for no longer than 24 h, such as , , , , and MKP-1, MMP-8, nerve growth factor receptor (NGFR). Similar alterations were observed in three genes (, , ) in the peripheral blood. The present results strongly suggest that these factors may serve as stress markers. The correlation of these factors in the blood and brain may enable the evaluation of stress-induced changes in the brain by blood analysis, which will contribute to preventing the onset of mental disorders.
评估精神障碍的前驱状态并预防其发作是困难的。由于应激可能是精神障碍的触发因素，因此识别应激反应生物标志物（应激标志物）来评估应激水平可能会有所帮助。我们迄今已经对各种应激后的大鼠大脑和外周血进行了组学分析，发现了许多对应激有反应的因子。在这项研究中，我们调查了相对适度应激对这些因子的影响，以确定应激标志物候选物。成年雄性 Wistar 大鼠接受 12 h、24 h 或 48 h 的浸水应激。应激导致体重减轻和血清皮质酮水平升高，并改变了焦虑和/或恐惧样行为。逆转录 PCR 和 Western blot 分析显示，应激不超过 24 h 就会显著改变海马基因和蛋白的表达，如 、 、 、 、MKP-1、MMP-8、神经生长因子受体（NGFR）。外周血中的三个基因（ 、 、 ）也观察到类似的改变。目前的结果强烈表明这些因子可能作为应激标志物。血液和大脑中这些因子的相关性可以通过血液分析来评估应激引起的大脑变化，这将有助于预防精神障碍的发作。
