Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cell Mol Neurobiol. 2022 May;42(4):1105-1123. doi: 10.1007/s10571-020-01003-0. Epub 2020 Nov 17.
Huntington disease (HD) is a progressive neurological disorder with dominant motor symptoms. It also has psychiatric manifestations, like anxiety and depression, that can emerge themselves before motor symptoms and impose a major burden on patients. Oxytocin (OXT) is a newly emerged treatment for disorders like autism and schizophrenia and recently is using to alleviate depression and anxiety. In the current study, we investigated the behavioral and molecular effects of OXT on the development of anxiety and depression in 3-nitropropionic acid (3-NP)-induced model of HD. Anxiety- and depression-like behaviors as well as the levels of oxytocin receptor (OXTR), metabotropic glutamate receptor (mGluR) 2, mGluR5, and glutathione (GSH) were measured in striatum, hippocampus, prefrontal cortex, and amygdala. Also, we questioned if sex had any modulatory effect. We found that 3-NP increased anxiety and depression compared to controls. It also reduced the levels of OXTR and mGluR2, increased mGluR5, and reduced GSH in studied brain regions. Pretreatment with OXT before the injection of 3-NP ameliorated anxiety and depression. Additionally, it protected the brain from developing low levels of OXTR, mGluR2, and GSH and high levels of mGluR5 in studied regions. The protective effects of OXT were similar between male and female animals. These data suggest that OXTR, mGluR2, mGluR5, and GSH may contribute to psychiatric manifestations of HD. In addition, pretreatment with OXT could prevent the mood changes in male and female rats.
亨廷顿病 (HD) 是一种进行性神经退行性疾病，以显性运动症状为特征。它还具有精神表现，如焦虑和抑郁，这些症状可能在运动症状出现之前出现，并给患者带来沉重负担。催产素 (OXT) 是一种新兴的自闭症和精神分裂症治疗药物，最近也被用于缓解抑郁和焦虑。在本研究中，我们研究了催产素对 3-硝基丙酸 (3-NP) 诱导的 HD 模型中焦虑和抑郁发展的行为和分子影响。在纹状体、海马体、前额叶皮层和杏仁核中测量了焦虑和抑郁样行为以及催产素受体 (OXTR)、代谢型谷氨酸受体 (mGluR) 2、mGluR5 和谷胱甘肽 (GSH) 的水平。此外，我们还研究了性别是否具有调节作用。我们发现，与对照组相比，3-NP 增加了焦虑和抑郁。它还降低了研究脑区中 OXTR 和 mGluR2 的水平，增加了 mGluR5 的水平，并降低了 GSH 的水平。在注射 3-NP 之前用 OXT 预处理可改善焦虑和抑郁。此外，它还保护大脑免受研究区域中 OXTR、mGluR2 和 GSH 水平降低和 mGluR5 水平升高的影响。OXT 的保护作用在雄性和雌性动物之间相似。这些数据表明，OXTR、mGluR2、mGluR5 和 GSH 可能与 HD 的精神表现有关。此外，OXT 的预处理可以预防雄性和雌性大鼠的情绪变化。
