Chen Jing, Luo Yanmin, Liang Xin, Kong Xiangru, Xiao Qian, Tang Jing, Qi Yingqiang, Tang Yong, Xiu Yun
Molecular Medicine Diagnostic and Testing Center, Institute of Life Science, Chongqing Medical University, Chongqing, 400016, P. R. China.
Department of Physiology, Chongqing Medical University, Chongqing, 400016, P. R. China.
Transl Neurosci. 2022 Oct 26;13(1):379-389. doi: 10.1515/tnsci-2022-0255. eCollection 2022 Jan 1.
-Methyl-d-aspartate receptor (NMDAR) signaling pathway has been implicated in the pathogenesis and treatment of depression. However, the role of NMDAR subunits in depression is still unclear. In this study, alteration in all seven NMDAR subunits in several brain areas of rats exposed to chronic unpredictable mild stress (CUMS), an animal model of depression, was detected. Our findings demonstrated that: (1) CUMS could induce a reduction in sucrose preference, an indicator of typical depression-like behaviors; (2) CUMS significantly reduced the NMDAR subunits of GluN2B and GluN3 in the medial prefrontal cortex (mPFC), but not altered all seven NMDAR subunits in hippocampus and corpus callosum of rats; (3) subunit composition of NMDARs in corpus callosum was different from that in mPFC, PFC and hippocampus; and (4) the mRNA expressions of GluN2B, GluN3A and GluN3B in mPFC as well as mRNA expression of GluN2C in corpus callosum were correlated to sucrose preference in rats. These findings suggested that GluN2B and GluN3 in mPFC may contribute to the pathophysiology of depression.
N-甲基-D-天冬氨酸受体（NMDAR）信号通路与抑郁症的发病机制及治疗有关。然而，NMDAR亚基在抑郁症中的作用仍不清楚。在本研究中，检测了暴露于慢性不可预测轻度应激（CUMS，一种抑郁症动物模型）的大鼠几个脑区中所有七种NMDAR亚基的变化。我们的研究结果表明：（1）CUMS可导致蔗糖偏好降低，这是典型抑郁样行为的一个指标；（2）CUMS显著降低了内侧前额叶皮质（mPFC）中GluN2B和GluN3的NMDAR亚基，但未改变大鼠海马体和胼胝体中所有七种NMDAR亚基；（3）胼胝体中NMDAR的亚基组成与mPFC、前额叶皮质和海马体中的不同；（4）mPFC中GluN2B、GluN3A和GluN3B的mRNA表达以及胼胝体中GluN2C的mRNA表达与大鼠的蔗糖偏好相关。这些发现表明，mPFC中的GluN2B和GluN3可能与抑郁症的病理生理学有关。
