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Behavioral features of mice fed with a cholesterol-enriched diet: Deficient novelty exploration and unaltered aggressive behavior

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Translational Neuroscience and Clinics 2016年第2期2卷 87-95页

作者： Ekaterina Veniaminova Raymond Cespuglio Nataliia Markova Niall Mortimer Chi wai Cheung harry w.steinbusch Klaus-Peter Lesch Tatyana Strekalova Department of Neuroscience School for Mental Health and Neuroscience Maastricht University Institute of General Pathology and Pathophysiology Russian Academy of Medical Sciences Faculty of Medicine Neuroscience research Center of Lyon C. Bernard University Department of Anatomy Guangzhou Medical University Laboratory of Biomolecular Screening Institute of Physiologically Active Compounds Russian Academy of Sciences Division of Molecular Psychiatry Laboratory of Translational Neuroscience Department of Psychiatry Psychosomatics and PsychotherapyUniversity of Wuerzburg Department of Anaesthesiology the University of Hong Kong Queen Mary Hospital

Objectives: Previous studies involving mice have demonstrated that a cholesterolenriched diet evokes liver steatosis, dystrophy, inflammation, and aspects of nonalcoholic fatty liver disease(NAFLD). These changes are accompanied by the activation of pro-inflammatory brain and liver molecular pathways, as well as anxiety and depressive-like behaviors. Given previously reported evidence for the neurobiological relationship between the above-mentioned molecular changes and abnormalities in coping with environmental stimuli, such as interactions with other individuals and new environmental contexts, we hypothesized that novelty exploration and aggressive behavior are affected in a mouse NAFLD model. Methods: To test this hypothesis, young female C57BL/6J mice were fed with a regular chow or a diet containing 0.2% cholesterol for 3 weeks. The mice were then assessed for new object and novel cage exploration, and social interaction in a food competition test. Results: we found reduced object exploration in mice on the cholesterol-enriched diet. This reduction was not related to whether the new object was placed in an anxiogenic or non-anxiogenic environment. These changes were accompanied by diminished exploration of the new environment in a novel cage, and delayed approach to food after a period of food deprivation. Mice on the regular chow or cholesterolenriched diet showed no differences in aggressive behavior towards a counter-partner in a food competition test. Food intake and body weight did not differ between the groups, thus, excluding their potential as confounders in the measured behaviors. Conclusions: we conclude that a diet enriched with cholesterol reduces novelty exploration irrespective of the anxiogenic level of the environment and does not induce aggressive behavior in female mice.

关键词： western diet cholesterol novelty exploration aggression mouse

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A study of the effects of 3,5-diiodo-L-thyronine in the tail suspension and forced swim models of depression

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Translational Neuroscience and Clinics 2016年第2期2卷 96-107页

作者： Nataliia Markova Anton Chernopiatko Aslan Kubatiev Sergey Bachurin harry M.w.steinbusch Tatyana Strekalova Laboratory of Biomolecular screening Institute of Physiologically Active Compounds Russian Academy of Sciences Laboratory of Cognitive dysfunctions Federal State Budgetary Scientific Institution "Institute of General Pathology and Pathophysiology" Department of Neuroscience School for Mental Health and Neuroscience Maastricht University Section of Neuropharmacology Research

Objectives: Recent findings have further highlighted the role of the thyroid system in the pathophysiology of depression and revealed new physiologically relevant elements of the thyroid system. Our previous study showed an antidepressant-like effect of 3,5-diiodo-L-thyronine(T2), which was previously considered to be a physiologically inactive molecule, in mice. Here, we aimed to investigate the antidepressant-like effects of T2 further. Methods: we studied the effects of bolus injections of T2 to C57Bl6 J mice at doses of 0.25 or 0.75 mg/kg with the tail suspension and forced swim models. The effects of the higher dose were investigated in CD1 mice in the forced swim test. Potential behavioral effects of these treatments were also studied using the novel cage and dark-light box ***: A reduction of depressive-like behavior was found in mice treated with 0.75 mg/kg of T2 in the tail suspension test, but not in the forced swim test. Locomotion and anxiety variables were unaltered following treatment with T2. There were no significant changes after bolus administration of 0.25 mg/kg T2 in either test for depressive-like behavior. Thus, bolus injection of T2 at the dose 0.75 mg/kg can induce antidepressant-like effects without affecting other behaviors. Conclusions: A discrepant result in the forced swim test may be due to its different sensitivity to T2 compared with the tail suspension paradigm. Furthermore, the development of procedural modifications of this model can be useful in its application in pre-clinical studies.

关键词： forced swim test tail suspension test depression animal models thyroid hormones

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Effects of voluntary imipramine intake via food and water in paradigms of anxiety and depression in naive mice

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Translational Neuroscience and Clinics 2016年第3期2卷 172-182,149页

作者： Joao Pedro Costa-Nunes Anastassia Bakhmet Margarida Araújo-Correia Andreia Barbosa Valenca Tatyana Strekalova harry w.M.steinbusch School for Mental Health and Neuroscience Maastricht University Center for Neuroscience and Cell Biology Universidade de CoimbraFaculdade de MedicinaRua Larga Centro de Biologia Ambiental Faculdade de Ciências da Universidade de Lisboa Department of Human Anatomy Moscow State Medical University Centro de Estudos de Doencas Crónicas(CEDOC) Edifício CEDOCⅡRua Camara Pestana Centro Interdisciplinar de Investigacao em Saúde Animal(CIISA) Faculdade de Medicina VeterináriaAlameda da Universidade Técnica

Objective: we sought to investigate the efficacy of oral dosing in mice with imipramine(7mg/kg/day) via water or in food pellets, and to compare its effects in the paradigms of learned helplessness, locomotion, hedonic state, and anxiety. Methods: water and food consumption were measured to determine daily imipramine dosage in C57BL/6N mice. Next, baseline scores for O-maze, dark/light box, and sucrose tests were measured. Mice were then subjected to a 4-week treatment of voluntary ingestion of drinking water or food pellets containing imipramine. Lastly, all groups were subjected to novel cage, open field, O-maze, dark/light box, sucrose test, and forced swim test to assess the effects of the treatment. Results: In na?ve mice, imipramine delivered via food, induced a reduction of total floating and increased latency in the forced swim test, i.e., antidepressant-like effects. No other significant effects were found. Dosing with water did not change behavior in the forced swim, sucrose preference test, anxiety, or locomotor paradigms, but increased exploration in the novel cage. Conclusions: Voluntary ingestion is an effective method of chronic dosing with imipramine in na?ve mice. Delivery of imipramine with food pellets elicits antidepressant-like effects in the forced swim test, with no effects on anxiety, locomotion, or preference behaviors. In contrast, no such effects were observed with treatment via drinking water, suggesting that a higher dose may be required. Our work argues for a broader use of oral delivery using food-treated pellets, in small rodent models of pre-clinical depression. It may substantially improve animal welfare and overcome potential confounds in translational research, which are frequently associated with adverse chronic invasive pharmacotherapies.

关键词： pre-clinical models depression anxiety oral dosing animal welfare

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长时程深部脑刺激外侧苍白球对转基因Huntington病大鼠认知和运动的影响(英文)

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神经解剖学杂志 2006年第3期22卷 275-280页

作者：曹春燕 Yasin Temel Arjan Blokland Veerle Visser-Vandewalle harry w.M. steinbusch 陈生弟刘振国上海交通大学医学院附属瑞金医院神经病学研究所上海200025 马斯特里赫特大学心理学系马斯特里赫特大学医院神经外科马斯特里赫特大学欧洲神经科学研究院上海交通大学医学院附属新华医院神经内科上海200092

我们研究了深部脑刺激(deep brain stimulation, DBS)对转基因Huntington病大鼠认知能力和运动功能的影响。实验结果表明:电极植入手术能改善Huntington病大鼠的认知能力,例如:在选择反应时间实验(choice reaction time task,CRT task)... 详细信息

我们研究了深部脑刺激(deep brain stimulation, DBS)对转基因Huntington病大鼠认知能力和运动功能的影响。实验结果表明:电极植入手术能改善Huntington病大鼠的认知能力,例如:在选择反应时间实验(choice reaction time task,CRT task)中,反应准确率增加,偏倚率减少。但对不同基因型大鼠,改善程度相同。在对大鼠外侧苍白球部(GPe)进行长时间深部脑刺激后,反应准确率增加,不同基因型大鼠的增加幅度有所不同。另外,深部脑刺激后, CRT实验中的运动时间和反应时间并没有变化。但是纯合子大鼠的舞蹈样运动明显改善。本研究结果表明深部脑刺激转基因Huntington病大鼠的GPe能明显改善其认知能力和运动功能,这预示着DBS在Huntington病的治疗中将有很大的应用前景。

关键词：深部脑刺激选择反应实验转基因Huntington病大鼠外侧苍白球

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高频电刺激苍白球外侧部改善转基因亨廷顿病大鼠认知和运动功能障碍

高频电刺激苍白球外侧部改善转基因亨廷顿病大鼠认知和运动功能障...

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第九次全国神经病学学术大会

作者：曹春燕 Yasin temel Arjan Blokland harry steinbusch 陈生弟刘振国上海交通大学医学院附属瑞金医院神经内科欧洲神经科学研究生院马斯特利赫特大学上海交通大学医学院附属新华医院神经内科

目的:亨廷顿病是一种常染色体显性遗传性神经系统变性疾病,突变基因IT15编码区的CAG重复片断增多导致纹状体内神经细胞变性坏死,患者表现渐进性发展的认知和运动功能障碍,认知功能障碍症状通常早发于运动障碍。尽管药物治疗可以改善运...

目的:亨廷顿病是一种常染色体显性遗传性神经系统变性疾病,突变基因IT15编码区的CAG重复片断增多导致纹状体内神经细胞变性坏死,患者表现渐进性发展的认知和运动功能障碍,认知功能障碍症状通常早发于运动障碍。尽管药物治疗可以改善运动功能障碍,但对认知功能障碍并无显著疗效。研究表明苍白球外侧部(GPe)兴奋性的改变与亨廷顿患者的认知和运动功能障碍有关系。在本实验中,我们研究深部脑刺激GPe是否可以改善转基因亨廷顿病大鼠的认知和运动功能障碍。方法:实验所应用的转基因亨廷顿病(tgHD)大鼠携带51个CAG重复片断的huntingtin cDNA,具有与亨廷顿患者相似的神经病理改变及渐进发展的认知和运动功能障碍。通过训练转基因亨廷顿病大鼠完成选择反应时间(CRT) 任务,以确定转基因亨廷顿大鼠是否有时间和基因型依赖性认知和运动功能障碍,然后将刺激电极植入大鼠双侧GPe,给予不同强度的高频电刺激(130Hz／60us／3,30,150uA),同时训练其完成CRT任务,观察刺激tgHD大鼠的GPe对是否纠正其在执行CRT任务时所表现的认知和运动功障碍。另外还观察高频电刺激是否对其特征性颈部舞蹈样运动障碍有改善。结果:tgHD大鼠在执行CRT任务时的不成熟反应显著多于wT大鼠(p<0．05),刺激GPe明显减少两组动物的不成熟反应 (p<0．01)。对基因型与刺激间的相互影响分析表明:与野生型大鼠相比,刺激对转基因亨廷顿大鼠有更显著的影响(p< 0．01)。30uA中等强度的刺激减少不成熟反应的程度最为明显。tgHD大鼠的反应准确率比野生型大鼠的反应准确率低,但没有显著意义(p<0．08),刺激并不能影响反应准确率。高频电刺激增加大鼠在执行运动反应时间任务时的反应时间(p< 0．01),不同的刺激强度对野生型大鼠和tgHD大鼠的影响未见不同。在20个月龄时,tgHD大鼠的颈部出现突发、快速并非规律性的异常运动,野生型大鼠并未表现运动障碍。刺激显著减少tgHD大鼠的异常运动(p<0．05),高强度的刺激(150uA) 减少幅度最大。结论:本研究表明高频电刺激GPe可以用于纠正亨廷顿病的认知和运动功能障碍。高频电刺激可以有效减少不成熟反应,不成熟反应表明反应抑制能力下降,反应抑制能力下降是亨廷顿病认知功能障碍的主要特点。另外,深部脑刺激GPe减轻了颈部舞蹈样运动症状,然而,相对于认知功能障碍,对运动障碍的治疗需要较高的刺激强度。这反映了皮层-基地节-丘脑皮层边缘系统环路和运动环路间的差别。

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