Efficacy of agomelatine on sleep disorders and lateral habenula neuronal activity in chronic restraint stress depression model mice.

IF 3.5 3区 医学 Q2 NEUROSCIENCES
Zhuojun Kang, Zhenzhen Zheng, Wenli Guo
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Abstract

Background: Sleep disorders (SD) are one of the common manifestations of depression patients. This article aimed to explore the effect of Agomelatine (Ago) on SD in chronic restraint stress (CRS) depression model mice and its effect on the activity of neurons in the lateral habenula (LHb).

Methods: 30 C57BL/6 J mice were divided into normal (C57BL/6 J) group, CRS group, and Ago group. CRS experiment was used to establish the depression model, and Ago was used to treat CRS mice. Based on behavioral tests in mice and electrophysiology record, SD and LHb neuron activity were assessed. The expression levels of brain-derived neurotrophic factor (BDNF) and nuclear phosphoprotein (c-Fos) in LHb were detected by Western blot (WB).

Results: As against the CRS group, the Ago group had a reduction in the immobility time during forced swimming training and an increase in the preference for sucrose in the sucrose preference test; The expression levels of c-Fos and BDNF proteins in the LHb neurons of the Ago group mice were lower than those in the CRS group (P < 0.05), and the values approached the levels of the normal control group. In both dark and light environments, the rapid eye movement (REM) sleep duration of the CRS group mice was significantly longer than that of the normal control group (P < 0.05).

Conclusion: It was concluded that Ago may intervene in the depressive-like behavior and overall sleep patterns of CRS depression model mice by regulating the activity of LHb neurons and inhibiting the neuroinflammatory process. This provides a potential drug target for the development of new treatment strategies for depression.

Abstract Image

阿戈美拉汀对慢性束缚应激抑郁模型小鼠睡眠障碍和外侧哈文神经元活动的疗效
背景:睡眠障碍(SD)是抑郁症患者的常见表现之一:睡眠障碍(SD)是抑郁症患者的常见表现之一。方法:将30只C57BL/6 J小鼠分为正常(C57BL/6 J)组、CRS组和Ago组。CRS实验用于建立抑郁模型,Ago用于治疗CRS小鼠。根据小鼠的行为测试和电生理记录,评估SD和LHb神经元的活性。Western印迹(WB)检测了脑源性神经营养因子(BDNF)和核磷蛋白(c-Fos)在LHb中的表达水平:结果:与CRS组相比,Ago组小鼠在强迫游泳训练中的静止时间缩短,在蔗糖偏好试验中对蔗糖的偏好增加;Ago组小鼠LHb神经元中c-Fos和BDNF蛋白的表达水平低于CRS组(P 结论:Ago组小鼠在强迫游泳训练中的静止时间缩短,在蔗糖偏好试验中对蔗糖的偏好增加;Ago组小鼠在强迫游泳训练中的静止时间缩短,在蔗糖偏好试验中对蔗糖的偏好增加:结论:Ago可通过调节LHb神经元的活性和抑制神经炎症过程,干预CRS抑郁模型小鼠的抑郁样行为和整体睡眠模式。这为开发新的抑郁症治疗策略提供了潜在的药物靶点。
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来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
期刊介绍: Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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