Rapid Eye Movement Sleep Deprivation Combined With Fluoxetine Protects Against Depression-Induced Damage and Apoptosis in Rat Hippocampi via A1 Adenosine Receptor.

Xuan Ju,Zhonglin Tan,Pan Yan,Chunyan Zhu,Jiezheng Dong,Xiwen Hu,Shengdong Wang

doi:10.3389/fpsyt.2021.599399

Xuan Ju, Zhonglin Tan + Show 5 more

Open Access

https://doi.org/10.3389/fpsyt.2021.599399

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Abstract

Background: Rapid eye movement sleep deprivation (REMSD) and fluoxetine affect depression, yet the detailed molecular mechanisms were not clear.Methods: 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.Results: 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.Conclusion:REMSD combined with fluoxetine protected rats against depression-induced damage and apoptosis in the hippocampus via the A1 adenosine receptor, providing a possible treatment strategy for depression.

Highlights

Depression has been recognized as one of the most significant causes of emotional suffering and a factor affecting the morbidity of several medical disorders [1, 2]
REM sleep deprivation (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
REMSD combined with fluoxetine protected rats against depression-induced damage and apoptosis in the hippocampus via the A1 adenosine receptor, providing a possible treatment strategy for depression

Summary

Introduction

Depression has been recognized as one of the most significant causes of emotional suffering and a factor affecting the morbidity of several medical disorders [1, 2]. Antidepressants have been acknowledged and used as the standard treatment for major depressive disorders (MDDs); their efficacy tends to be variable and incomplete [12]. As one of the most prescribed antidepressants, fluoxetine plays a vital role in MDD treatment and has been approved for clinical use, with effects on neurocognitive functions in adults with depression [13, 14]. The combined therapy of TSD and fluoxetine has been used for the treatment of depression [15]. The combined therapy of REM sleep deprivation (REMSD) and fluoxetine used for the treatment of depression and the potential mechanism has been needed to be explored. Rapid eye movement sleep deprivation (REMSD) and fluoxetine affect depression, yet the detailed molecular mechanisms were not clear

Methods

Results

Conclusion