Pei Chen-Di, Zhang Lu-Lu, Fei Peng-Ge, Gu Shi-Na, Li Wen-Qiang, Mu Jun-Lin, Wang Xu-Sheng, Wang Wen-Sheng, Zhang Xiang-Yang, Zhang Zhao-Hui, Song Jing-Gui
Department of Neurology, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
Biomed Rep. 2019 Aug;11(2):51-58. doi: 10.3892/br.2019.1225. Epub 2019 Jun 24.
Aryl hydrocarbon receptor nuclear translocator protein 2 (ARNT2), a member of the basic helix-loop-helix superfamily of transcription factors, may serve a vital role in neuronal survival and cell proliferation via formation of heterodimers with hypoxia-inducible factor-1α. Previous studies indicated that ARNT2 levels were elevated in the brains of ischemic rats; however, the involvement of ARNT2 in post-stroke depression (PSD) rats is not well understood. Therefore, the present study aimed to investigate the levels of ARNT2 in the hippocampi of PSD rats, and to clarify the potential association between ARNT2 and behavioral performance. A PSD rat model was established by middle cerebral artery occlusion (MCAO) followed by a 4-week chronic unpredictable mild stress (CUMS) regimen. A sucrose preference test and open field test (OFT) were conducted, and body weight was measured. In addition, reverse transcription-polymerase chain reaction and immunohistochemistry were performed to measure ARNT expression. Results indicated that MCAO+CUMS rats had lower weight gain, consumed less sucrose and moved less compared with controls. Furthermore, the mRNA and protein levels of ARNT in MCAO+CUMS rats were increased compared with in controls. The sucrose preference index and horizontal movement distance in the OFT were positively correlated with ARNT mRNA level. Thus, from these findings it was suggested that ARNT2 may be positively associated with improvement of cognitive impairment, and therefore may be a potential target in PSD treatment.
芳烃受体核转运蛋白2(ARNT2)是转录因子碱性螺旋-环-螺旋超家族的成员之一,可能通过与缺氧诱导因子-1α形成异二聚体在神经元存活和细胞增殖中发挥重要作用。先前的研究表明,缺血大鼠大脑中ARNT2水平升高;然而,ARNT2在中风后抑郁症(PSD)大鼠中的作用尚不清楚。因此,本研究旨在探讨PSD大鼠海马中ARNT2的水平,并阐明ARNT2与行为表现之间的潜在关联。通过大脑中动脉闭塞(MCAO),然后进行为期4周的慢性不可预测轻度应激(CUMS)方案建立PSD大鼠模型。进行蔗糖偏好试验和旷场试验(OFT),并测量体重。此外,进行逆转录-聚合酶链反应和免疫组织化学以测量ARNT表达。结果表明,与对照组相比,MCAO+CUMS大鼠体重增加较少,蔗糖消耗量较少,活动较少。此外,与对照组相比,MCAO+CUMS大鼠中ARNT的mRNA和蛋白质水平升高。OFT中的蔗糖偏好指数和水平移动距离与ARNT mRNA水平呈正相关。因此,从这些发现表明,ARNT2可能与认知障碍的改善呈正相关,因此可能是PSD治疗的潜在靶点。