Hou YuanYuan, Wang YunLei, Song ShaoFei, Zuo Yao, Zhang HaoJie, Bai Chen, Zhao HaiTao, Zhang Tong
School of Rehabilitation Medicine, Capital Medical University, Beijing 100068, China; Lab of Brain Injury Repair and Rehabilitation, China Rehabilitation Science Institute, Beijing 100068, China; Department of Neurological Rehabilitation, Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing 100068, China.
Lab of Brain Injury Repair and Rehabilitation, China Rehabilitation Science Institute, Beijing 100068, China; Department of Neurological Rehabilitation, Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing 100068, China; Shandong University, Shandong 250012, China.
Exp Neurol. 2022 Jan;347:113908. doi: 10.1016/j.expneurol.2021.113908. Epub 2021 Oct 26.
Long-term shift work can cause circadian misalignment, which has been linked to anxiety and depression. However, the associated pathophysiologic changes have not been described in detail, and the mechanism underlying this association is not fully understood. To address these points, we used a rat model of CM induced by long-term variable photoperiod exposure [L-VP] (ie, for 90 days). We compared the numbers of neurons, astrocytes, and dendritic spines; dendrite morphology; long-term potentiation (LTP), long-term depression (LTD) and paired-pulse ratio (PPR); expression of glutamate receptor [N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)] subunits and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC); and the anxiety and depression behaviors between rats in the circadian misalignment (CM) and circadian alignment (CA, with normal circadian rhythm) groups. The results showed that L-VP reduced the number of neurons and astrocytes in the mPFC and decreased the number of dendritic spines, dendrite complexity, LTP, LTD, PPR, and expression of glutamate receptors (GluR1, GluR2, GluR3, NMDAR2A, and NMDAR2B) and BDNF in the mPFC. L-VP also induced anxiety and depression-like behaviors, as measured by the open field test, elevated plus-maze, sucrose preference test, and forced swim test. These results suggest that CM induces a loss of neurons and astrocytes and synaptic damage in surviving pyramidal cells in the mPFC might be involved in the pathophysiology of anxiety and depression.
长期轮班工作会导致昼夜节律失调，这与焦虑和抑郁有关。然而，相关的病理生理变化尚未详细描述，这种关联的潜在机制也尚未完全了解。为了解决这些问题，我们使用了长期可变光周期暴露（即90天）诱导的昼夜节律失调大鼠模型[L-VP]。我们比较了内侧前额叶皮质（mPFC）中神经元、星形胶质细胞和树突棘的数量；树突形态；长时程增强（LTP）、长时程抑制（LTD）和双脉冲比率（PPR）；谷氨酸受体[N-甲基-D-天冬氨酸受体（NMDAR）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）]亚基和脑源性神经营养因子（BDNF）的表达；以及昼夜节律失调（CM）组和昼夜节律正常（CA）组大鼠之间的焦虑和抑郁行为。结果表明，L-VP减少了mPFC中神经元和星形胶质细胞的数量，减少了树突棘的数量、树突复杂性、LTP、LTD、PPR以及mPFC中谷氨酸受体（GluR1、GluR2、GluR3、NMDAR2A和NMDAR2B）和BDNF的表达。L-VP还诱导了焦虑和抑郁样行为，通过旷场试验、高架十字迷宫试验、蔗糖偏好试验和强迫游泳试验来测量。这些结果表明，昼夜节律失调会导致神经元和星形胶质细胞丢失，mPFC中存活锥体细胞的突触损伤可能参与了焦虑和抑郁的病理生理过程。
