Ju Xuan, Wang Shengdong, Yan Pan, Zhu Chunyan, Hu Xiwen, Dong Jiezheng, Tan Zhonglin
Psychiatric Department, Hangzhou Seventh People's Hospital, Mental Health Center of Zhejiang University School of Medicine, Hangzhou, China.
Molecular Biology Laboratory, Hangzhou Seventh People's Hospital, Mental Health Center of Zhejiang University School of Medicine, Hangzhou, China.
Front Psychiatry. 2021 Jul 16;12:599399. doi: 10.3389/fpsyt.2021.599399. eCollection 2021.
Rapid eye movement sleep deprivation (REMSD) and fluoxetine affect depression, yet the detailed molecular mechanisms were not clear. Rat depression chronic unpredictable stress was constructed, and the body weight of rats was measured. The efficacy of REMSD and fluoxetine on the pleasure experience, exploration, and cognition of rats with depression was determined by the Sucrose preference test, the open field test, and Morris water task, respectively. The effects of REMSD and fluoxetine on depression-induced damage and apoptosis in rat hippocampi were detected using hematoxylin-eosin staining and terminal transferase-mediated biotin 2'-deoxyuridine, 5'-triphosphate nick end labeling. A1 adenosine receptor content was measured by immunohistochemistry. Relative expressions of the A1 adenosine receptor, proteins related to apoptosis (B Bcl-2-associated X protein; B-cell lymphoma 2), phosphoinositide 3-kinase, P38 mitogen-activated protein kinase, cFos, and adenosine deaminase RNA specific two were quantified by quantitative real-time polymerase chain reaction and Western blot as needed. Depression decreased rat weight. REMSD combined with fluoxetine increased body weight, prompted rat behavior, alleviated depression-induced damage, attenuated apoptosis, and promoted A1 adenosine receptor level in rat hippocampi. Furthermore, the combined therapy upregulated expressions of A1 adenosine receptor, B-cell lymphoma 2, and phosphoinositide 3-kinase but downregulated those of B-cell lymphoma 2-associated X protein, P38 mitogen-activated protein kinase, cFos, and adenosine deaminase RNA specific 2 in the hippocampi of rats with depression. REMSD combined with fluoxetine protected rats against depression-induced damage and apoptosis in the hippocampus the A1 adenosine receptor, providing a possible treatment strategy for depression.
快速眼动睡眠剥夺（REMSD）和氟西汀会影响抑郁症，但具体分子机制尚不清楚。构建大鼠慢性不可预测应激抑郁模型，并测量大鼠体重。分别通过蔗糖偏好试验、旷场试验和莫里斯水迷宫任务来确定REMSD和氟西汀对抑郁大鼠愉悦体验、探索行为和认知的影响。采用苏木精-伊红染色和末端转移酶介导的生物素2'-脱氧尿苷5'-三磷酸缺口末端标记法检测REMSD和氟西汀对大鼠海马抑郁诱导损伤和细胞凋亡的影响。通过免疫组织化学法检测A1腺苷受体含量。根据需要，通过定量实时聚合酶链反应和蛋白质免疫印迹法对A1腺苷受体、凋亡相关蛋白（B Bax；Bcl-2）、磷酸肌醇3-激酶、P38丝裂原活化蛋白激酶、cFos和腺苷脱氨酶RNA特异性2的相对表达进行定量分析。抑郁症会降低大鼠体重。REMSD联合氟西汀可增加体重、促进大鼠行为、减轻抑郁诱导的损伤、减弱细胞凋亡并提高大鼠海马中A1腺苷受体水平。此外，联合治疗上调了抑郁大鼠海马中A1腺苷受体、Bcl-2和磷酸肌醇3-激酶的表达，但下调了Bax、P38丝裂原活化蛋白激酶、cFos和腺苷脱氨酶RNA特异性2的表达。REMSD联合氟西汀可保护大鼠免受抑郁诱导的海马损伤和细胞凋亡，通过A1腺苷受体发挥作用，为抑郁症提供了一种可能的治疗策略。
