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Effect and regulation ofα-dstroglycan glyco⁃sylation on chronic social defeat induced depressive-like behaviors of mice

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中国药理学与毒理学杂志 2021年第9期35卷 693-694页

作者： LI Yu-ke WANG Fang Department of pharmacology School of basic medicineTongji Medical CollegeHuazhong Uni-versity of Science and TechnologyWuhan 430030China

OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high *** research⁃es have reported that hypoglycosylation ofα-DG is associated with the pathophysiology of diseas⁃es,especially muscular dystrophy,but little is known about major depressive disorder(MDD).Like-acetylglucosaminyl transferase(Large)is a key enzyme for glycosylation ofα-DG,which mainly modifies two points in the middle domain ofα-DG:Thr-317 and ***α-DG(GLY-α-DG)can bind with high affinity to extracellular matrix(ECM)molecules that con⁃tain laminin globular(LG)domains,including per⁃lecan,agrin and *** is mainly derived from neurons rather than glial *** cultured hippocampal neurons,it was found that agrin could regulate the homeostatic plasticity of inhibi⁃tory neurons by acting on GLY-α-*** mice are transgenetic models for the investigation of Duchenne muscular *** studies have shown that the expression of GLY-α-DG in the peripheral and brain tissues of Mdx mice is significantly *** mice show cognitive impairment and high levels of *** this study,we employed chronic social defeat stress(CSDS)to establish an animal model of depression and detected the expression of GLY-α-DG among the brain areas associated with the pathophysiology of *** So⁃cial interaction test(SIT)and sucrose preference test(SPT)were used to evaluate depressive-like *** field(OF)and elevated plus maze(EPM)test were used to determine the anxiety-like behavior of Mdx ***-sup⁃pressed feeding test(NSFT)forced swim test(FST)and tail suspension test(TST)were used to detect the depressive-like behavior of Mdx *** object recognition test(NOR)was applied to evaluate the cognition of Mdx *** social defeat stress was used to explore the susceptibility to stress in Mdx ***

关键词： α-dstroglycan depressive-like behav⁃iors social defeat

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Tree shrew models:A chronic social defeat model of depression and a one-trial captive conditioning model of learning and memory

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Zoological Research 2011年第1期32卷 24-30页

作者：王静周启心田孟杨跃雄徐林中国科学院和云南省动物模型与人类疾病机理重点实验室中国科学院昆明动物研究所云南昆明650223 中国科学院研究生院北京100049

Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human *** this paper,we report on a social defeat model of depression in tree shrew（Tupaia belangeri chinensis）.Two male tree shrews were housed in a pair-cage consisting of two independent cages separated by a wire mesh partition with a door connecting the two *** one week adaptation,the connecting door was opened and a brief fighting occurs between the two male tree shrews and this social conflict session consisted of 1 h direct conflict（fighting） and 23 h indirect influence（***,visual cues） per day for 21 *** defeated tree shrew was considered the *** with na？ve animals,subordinate tree shrews at the final week of social conflict session showed alterations in body weight,locomotion,avoidance behavior and urinary cortisol ***,these alterations persisted for over two *** also report on a novel captive conditioning model of learning and memory in tree *** automatic trapping cage was placed in a small closed room with a freely-moving tree *** the first four trials,the tree shrew was not trapped when it entered the cage and ate the bait apple,but it was trapped and kept in the cage for 1 h on the fifth *** was defined as the time between release of the tree shrew and when it entered the captive *** during the five trials indicated adaptation.A test trial 24 h later was used to measure whether the one-trial trapping during the fifth trial could form captive *** shrews showed much longer trapping latencies in the test trial than the adaptation *** N-methyl-d-aspartate（NMDA） receptor antagonist MK-801（0.2 mg/kg,i.p.）,known to prevent the formation of memory,did not affect latencies in the adaptation trails,but did block captive memory as it led to much shorter trapping latencies compared to saline treatment in the test tr

关键词： social defeat Depression Captive conditioning Learning and memory Tree shrew

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Sini Powder extract produces antidepressant-like effects in a chronic social defeat stress model of depression in tree shrews

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Journal of Chinese Pharmaceutical Sciences 2016年第6期25卷 458-465页

作者：韦姗姗杨和金黄加文陆雪萍彭玲芳王庆国北京中医药大学基础医学院北京100029 云南省药物研究所药物筛选中心云南昆明650111

Sini Power（SP） is a famed traditional Chinese formula that has long been used to treat depression. Here, we investigated the effects and possible mechanisms of SP extract on an established model of depression： chronic stressed tree shrew, which mimics the human condition of social stress. The animals were divided into 4 groups. Except for the na？ve group, the other animals were subjected to daily social defeat stress for 5 weeks, and during the last 4 weeks treated with SP extract（3.6 g/kg/d）, fluoxetine（15 mg/kg/d）, and vehicle, respectively. The results showed that SP extract could reverse body weight loss to a certain extent and reduce the levels of urine/serum cortisol that were initially increased by chronic social defeat. In addition, SP extract increased hippocampus norepinephrine concentrations. Our data suggested that SP extract had positive effects on the main depression symptoms in the chronic stressed tree shrew model and that it may be used to help control hypothalamic-pituitary-adrenal axis hyperactivity.

关键词： Chronic stress Tree shrews social defeat Sini Powder extract Hypothalamic-pituitary-adrenal axis

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SB-334867 Improves Anxiety-Like Behavior in social defeat Mouse by Regulating HPA Axis

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神经药理学报 2019年第4期 24-25页

作者： ZHANG Yun-peng CHEN Long CHEN Dan-mei WANG Cui-ting WANG Xiao-kun LI Bing Research Center for Clinical Medicine Jinshan Hospital Affiliated to Fudan University The Institute of Neurology The Academy of Integrative Medicine of Fudan University Department of Neurology Jinshan Hospital Affiliated to Fudan University

Objective:Depression is one of the major disease and becomes a public medical health problem worldwide. Current antidepressant drugs typically require weeks to months before a response to the treatment can be observed in the patients with major depressive disorders( MDD). Therefore,development of novel agents that produce a rapid antidepressant response represents a major unmet medical need for the treatment of MDD. Recently,several studies indicate that Orexin antagonists,and in particular selective OxR1( Orexin-1 receptor) antagonists,can reduce drug-seeking at doses that have minimal effects on natural reward-seeking behavior. With respect to the potential use of orexin receptor antagonists for anxiety and depression,we proposed the use of OxR1 antagonist( SB-334867) in the treatment of depressive disorder. We observed the effects of SB-334867 on behavioral stress reactivity and the plasma levels of ACTH and cortisol in social defeat mouse depression model,confirming that SB-334867 can improve the anxiety-like behavior of socially failing mice by modulating the HPA axis. Methods:The social defeat mouse(C57 BL/6 J) model was prepared according to the method of Tatsuhiko Goto et al.,and SB-334867( 2 mg·kg-1) was injected through the tail vein. Elevated O maze test and social Avoidance Test were performed on the social defeat mouse,and the plasma levels of ACTH and cortisol were detected by Elisa. Besides,Western blot was used to detect the changes of Orexin-A and Orexin-1 receptor in the hypothalamus. Results:The social interaction ratio( SI ratio) illustrated that the depression animal model induced by modified chronic social defeat stress is reliable. The SI ratio of the model group,the vehicle group and the drug-administered group were significantly lower than those of the control group;however,after 14 days of intravenous injection of SB-334867,the SI ratio of the mice in the drug-administered group was significantly higher than that in the model group and the

关键词： social defeat anxiety Orexin receptor HPA axis

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Selectively activate Kv7.4channel in DRN 5-HT neurons reverses depression-like behavior in social defeat model

Selectively activate Kv7.4channel in DRN 5-HT neurons revers...

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中国神经科学学会第十二届全国学术会议

作者： Chen Zhao Yingzi Wang Li Li Min Su Jing Wang Hailin Zhang Deparment of Pharmacology Hebei Medical University

Objective It’s well known that serotonergic system originating in dorsal raphe nuclei（DRN） play essential roles in the control of mood, the pharmacotherapy of anxiety and depression. Here we describe the crucial roles of Kv7.4 potassium channels in modulating the excitability of 5-HT neurons in DRN and the development of depressionlike behaviors in social defeat depression models. Methods（1） Whole-cell patch clamp was used to record Kv7 currents and elicited firing activity of DRN 5-HT neurons. And non-invasive loose-seal cell-attached patch clamp was used to record the spontaneous firing activity.（2） Cell types were identified via single-cell PCR.（3） The depression-like behaviors were measured by social interaction test and sucrose preference test. Results（1） Among the subunits of Kv7 channels, Kv7.4 selectively expressed in DRN 5-HT neurons.（2） Fasudil potently augments Kv7.4 current in DRN 5-HT neurons.（3） Kv7.4 activity modulates the excitability of DRN 5-HT neurons.（4） Fasudil reversed the depression-like behaviors in the social defeat models of depression. Conclusion Since the expression of Kv7.4 in the CNS is limited, selectively targeting Kv7.4 channel is likely to produce fewer side effects than non-selective Kv7 channel openers and, thus, Kv7.4 may offer an alternative novel target for treating depression.

关键词： Kv7.4 5-HT DRN social defeat depression-like behavior

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CDK5-mediated nuclear translocation of Sirt2 contributes to depressive-like behaviour induced by social defeat stress

CDK5-mediated nuclear translocation of Sirt2 contributes to ...

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中国神经科学学会第十二届全国学术会议

作者： Zheng Zhang Pei Zhang Guang-Jian Qi Feng-Juan Jiao Qing-Zhi Wang Jian-Guo Yan Feng He Qian Zhang Ze-Xi Lv Xiang Peng Hong-Wei Cai Bo Tian Department of Neurobiology Tongji Medical School Huazhong University of Science and Technology Nanyang Medical College Institute for Brain Research Huazhong University of Science and Technology

Objective Major depressive disorder（MDD） is a common, severe and recurrent psychiatric disorder worldwide;however, the underlying neuropathological mechanisms remain elusive. Histone deacetylases, such as sirtuins（Sirt）, appear to play an essential role in depression. Indeed, chronic stress decreased Sirt1 activity and downregulated Sirt1 gene expression in MDD;however, there is a paucity of literature on the role of Sirt2. We established a MDD mouse model in wild type and Sirt2 knockout C57 BL/6 mice using social defeat stress（SDS） to study the role of Sirt2. Methods social interaction, forced swimming, elevated plus maze, open field and sucrose preference tests were used for behavioural analyses. Western blotting and immunofluorescence were utilised to analyse Sirt2 protein. Tet Tag-pharmacogenetic method was used to study the regulation of ventral tegmental area（VTA）.Results SDS led to Sirt2 nuclear translocation in the amygdala, and blocking the phosphorylation of Sirt2 by CDK5 at serine residues 368 and 372 prevented SDS-induced Sirt2 nuclear import. We also discovered that this mechanism was involved in VTA-amygdala modulation. Conclusion These results suggest that CDK5 mediates Sirt2 nuclear translocation in the amygdala and contributes to the depressive-like behaviour induced by SDS.

关键词： CDK5 Sirt2 Major depressive disorder social defeat

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Repeated social defeat stress induces depressive-like and anxiety-like behaviours in mice

Repeated social defeat stress induces depressive-like and an...

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中国神经科学学会第十届全国学术会议

作者： Qiuqin Han Liu Yang Na Yue Xiaocang Zhu Bing Li Gencheng Wu Jin Yu Department of integrative medicine and neurobiology State key lab of medical neurobiologyInstitutes of brain scienceShanghai medical collegeFudan University

Objective The present research was designed to study the depressive-like and anxiety-like behaviours as well as the social interactions in a repeated social defeat stress,a mice model of *** In this model,C57BL/6J mice were repeatedly subjected to bouts of social defeat stress on 10 consecutive days by different larger and aggressive CD-1 *** 10 days of social defeat stress or control home cage housing,a battery of behavioral tests（i.e.,social interaction test,elevated plus-maze test,forced swimming test,sucrose preference test） were *** In social interaction test,susceptible mice spent significantly more time in the corner zone than in the interaction zone;meanwhile both control and resilient mice spent significantly more time in the interaction zone when CD-1 mouse as a target was ***,susceptible mice spent less time in open arms in elevated plus-maze test and had reduced struggling time and enhanced immobility time in forced swimming test,compared with control ***,the social defeat stress did not significantly lower the percentage of sucrose water the susceptible mice *** Repeated social defeat stress induced not only defeated and subordinate behavior but also some depressive-like and anxiety-like behaviors.

关键词： social defeat depression social interaction test elevated plus-maze test forced swimming test sucrose preference test

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social avoidance and anxiety-like behaviors induced by social defeat stress in adult male tree shrews

Social avoidance and anxiety-like behaviors induced by socia...

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中国神经科学学会第十届全国学术会议

作者： Rong-Jun NI Yu-Mian SHU Hui FANG Jing WANG Lin XU Jiangning ZHOU Chinese Academy of Science Key Laboratory of Brain Function and Diseases School of Life SciencesUniversity of Science and Technology of China Key Laboratory of Animal Models and Human Disease Mechanisms Chinese Academy of Sciences & Yunnan ProvinceKunming Institute of Zoology

Objective Adult male tree shrews（Tupaia belangeri chinensis） display an intense territoriality and live singly or in pairs in territories that they defend vigorously against intruding *** of two males in one cage may lead to a stable dominant-subordinate *** this study,we investigated the behavioral phenotype after social defeat stress and the underlying mechanisms in stress-related brain *** Before the sequence of behavioral tests,subordinate（SUB） and dominant（DOM） subgroups were identified according to the results of social behavioral analysis after social defeat stress in adult male tree *** Cortisol levels in plasma were measured by *** social stress for 2 months induced significant reduction of social interaction time of SUB（P＜0.05）.SUB showed significant reduction in distance moved following social-defeat stress（P＜0.05）.However,there is no significant difference in locomotor activity between SUB and DOM in the open field *** is a significant difference in social interaction ratio（time spent in the interaction zone in the presence of a social targel/time spent in interaction zone without a social target） between SUB and DOM（P＜0.05）.In the novelty-suppressed feeding,social stress significantly increased the feeding latency of SUB（P＜0.05）.In addition,there is a significant difference in mean distance from the center point of SUB and DOM to center point of food zone（P＜0.05）.However,there is no significant difference in sucrose preference and Cortisol levels in plasma between SUB and *** These results indicate that social defeat stress induces social avoidance and anxiety-like behaviors in subordinate tree shrews,which is not involved in HPA-axis activity.

关键词： social avoidance anxiety-like behavior social defeat tree shrew

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Resilience to the effects of social stress on vulnerability to developing drug addiction

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World Journal of Psychiatry 2022年第1期12卷 24-58页

作者： Claudia Calpe-López Maria A Martínez-Caballero Maria P García-Pardo Maria A Aguilar Department of Psychobiology University of ValenciaValencia 46010Spain Faculty of social and Human Sciences University of ZaragozaTeruel 44003Spain

We review the still scarce but growing literature on resilience to the effects of social stress on the rewarding properties of drugs of *** define the concept of resilience and how it is applied to the field of drug addiction *** also describe the internal and external protective factors associated with resilience,such as individual behavioral traits and social *** then explain the physiological response to stress and how it is modulated by resilience *** the subsequent section,we describe the animal models commonly used in the study of resilience to social stress,and we focus on the effects of chronic social defeat(SD),a kind of stress induced by repeated experience of defeat in an agonistic encounter,on different animal behaviors(depression-and anxiety-like behavior,cognitive impairment and addiction-like symptoms).We then summarize the current knowledge on the neurobiological substrates of resilience derived from studies of resilience to the effects of chronic SD stress on depressionand anxiety-related behaviors in ***,we focus on the limited studies carried out to explore resilience to the effects of SD stress on the rewarding properties of drugs of abuse,describing the current state of knowledge and suggesting future research directions.

关键词： Resilience Stress Depression Drug addiction Animal models social defeat

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Behavioral animal models of depression

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Neuroscience Bulletin 2010年第4期26卷 327-337页

作者：严华成曹雄 Manas Das 朱心红高天明南方医科大学神经生物学教研室广州510515

Depression is a chronic,recurring and potentially life-threatening illness that affects up to 20%of the population across the *** its prevalence and considerable impact on human,little is known about its *** of the major reasons is the restricted availability of validated animal models due to the absence of consensus on the pathology and etiology of ***,some core symptoms such as depressed mood,feeling of worthlessness,and recurring thoughts of death or suicide,are impossible to be modeled on laboratory ***,the criteria for identifying animal models of depression rely on either of the 2 principles：actions of known antidepressants and responses to *** review mainly focuses on the most widely used animal models of depression,including learned helplessness,chronic mild stress,and social defeat ***,the behavioral tests for screening antidepressants,such as forced swimming test and tail suspension test,are also *** advantages and major drawbacks of each model are *** prospective,new techniques that will be beneficial for developing novel animal models or detecting depression are discussed.

关键词： depression animal models learned helplessness chronic mild stress social defeat forced swimming test tail suspension test

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