这项工作是由美国国立卫生研究院支持的补助CA163640，CA166590和AG041250到LC。

下面所描述的程序已经批准了美国俄亥俄州立大学的机构动物护理和使用委员会（IACUC）。 1.准备丰富环境之前，房屋小鼠<ol><li>清洁和维护仪器。 <ol><li>通过洗笼运行大型铀浓缩仓（120厘米×90厘米×76厘米）。一个典型的动物笼子设施清洗协议包括5至6次的洗涤，最后到达周期82ºC。整个清洗大约需要40分钟。空气干燥仓。 <ol><li>如果大富集bin和任何其他壳体仪器，无法通过笼洗涤被发送，然后喷雾和擦拭用按照制造商的说明，杀孢子消毒剂的bin的内部。擦去用自来水浸湿的纸巾或30％乙醇和用干纸巾的bin摆脱从以前的任何消毒剂气味。 </li></ol></li><li>使用PLAS抽动油管，用圆顶型飞碟车轮，而在其他EE各种塑料笼般的玩具。通过笼洗洗这些玩具。如果您没有访问笼清洗的后续步骤1.1.1.1。 </li><li>使用金​​属转轮在EE。通过笼洗洗车轮。如果在车轮的涂料开始褪色，使得车轮变得嘈杂当动物在其上运行，将少量凡士林到车轮和阿克塞尔连接。 </li><li>使用木原木在EE。通过消除手工任何被褥或其他杂物清理干净的日志。然后，通过高压灭菌它们在干燥循环或纺织品周期，这达到121°C持续15分钟的温度杀菌日志。 </li><li>使用的29厘米×18厘米×12.5厘米和30.5厘米×19厘米×14厘米维度之间笼成保持进料和饮用导线rack.Cut空穴至少5厘米，直径从笼的前端底部的老鼠从EE进出的。通过清洁洗笼喂养这些笼子。 </li></ol></li><li>设置环境<ol><li>倒入¼英寸的玉米棒实验动物的床上用品到大仓富集。覆盖仓的整个地板表面的2-2.5厘米的床上用品的深度。 </li><li>将两个或三个日志中的仓的一个角落。在边角处日志隔离约1225厘米2的面积。通过日志隔离的区域，放三冰屋在顶部飞碟车轮。确保车轮未接触的bin，日志，或彼此的壁，以便有足够的空间供车轮自由旋转。 </li><li>拼凑的塑料管，以便多个臂从森特拉尔连接件分支出来。把这个管子在bin中间。 </li><li>在仓的两个角，将每个填充有相同寝具作为箱柜1馈送笼，并在馈送笼前部的孔应朝向仓的中心。在这些笼子里喂一个干净的食物和水线之上应放置于保持食物和水。不要将任何盖子上笼。放的食物和水的笼子里的电线。 </li><li>将三个金属轮子的箱子，虽然不是所有的彼此相邻。三种不同类型的车轮是一体11.5厘米车轮一20.5厘米轮，以及一个28厘米车轮。然后将4-5更多的塑料笼般的玩具或隧道贯穿富集仓。 </li><li>覆盖微型隔离过滤纸仓。用长尾夹滤纸夹到bin。 </li><li>新颖性是重要的EE。使用该设置作为EE的框架和变化的放置上述笼，对象和玩具以创建一个新的环境，为动物。 </li></ol></li></ol> 2.房屋的动物<ol><li>动物繁殖在常规实验室的住房，而不是EE实验。或者，将动物EE年龄早21天断奶后。基因型和耳朵打孔/标签动物前EE住房。 </li><li>当放置进入动物从笼子标准富集箱，放置在其一侧仓笼，使得动物可以从标准笼富集仓自由移动。不允许嵌套的材料被转移到富集箱。 </li><li>众议院10-20动物一样的年龄，性别，并在EE基因菌株。 </li></ol> 3.维护环境和观察小鼠在研究<ol><li>日报<ol><li>静静地观察动物的疾病或痛苦的迹象。如果有必要，轻轻地处理动物进一步检查健康状况。记录异常的观察和咨询卫生技术人员或兽医人员如果需要去除的实验动物显示条件。 </li><li>提供三重抗生物药膏小伤口结痂或局部治疗。如果动物需要因慢性疾病或伤害被删除，从实验安乐死取出的动物。如果动物满足了监督动物研究护理委员会或兽医早期切除的标准，不回动物回EE。 </li></ol></li><li>一个星期两次<ol><li>检查饲料和饮水的水平。确保饲料和水将持续在未来3-4天。整顿运行车轮和富集玩具使它们展开并且可以使用小鼠。更换任何过于肮脏。 </li></ol></li><li>周刊<ol><li>更换水瓶用干净的矿泉水瓶。重新排列在下面的第1.2节设置的方式浓缩设备。然而从此前一周的设置不同。 注意:如果一个实验要求从富集的环境中取出为活性的动物（记录体重，抽血，行为试验等 ），最好是重新排列的环境，而动物是远离富集仓。 </li><li>手工清洁的EE饲养笼或通过洗笼发送详见第1.1.5。更换食物和水持有干净的线架以及导线架。 </li><li>按照第2.2节的指令。当放置在浓缩的动物回来。现货必要时检查大型铀浓缩bin和清洁的休息，由舀出肮脏的垃圾和推广新的下跌干净的被褥。 </li></ol></li><li>双周<ol><li>在执行每周饲养，手工清洗的玩具或者通过发送洗笼在1.1.2节详述。如果需要的话，将小鼠在标准的微隔离器笼清洁所需的时间。 </li></ol></li><li>每月一次<ol><li>清洁大多数垃圾出移动富集玩具和饲养笼和舀出的垃圾。更换新鲜垫料。确保有床上用品，在笼子里的各个领域之一英寸。如果需要的话，将小鼠在标准的微隔离器笼清洁所需的时间。 </li></ol></li><li>每三个月（或在实验结束） <ol><li>删除所有的床上用品和玩具，干净，如第1.1.1节所述消毒富集仓。如果实验正在进行中，更换新的床上用品，饲养笼，玩具琳琅满目，然后返回小鼠到bin。 </li></ol></li><li>如果需要的研究机构，其中EE坐落更频繁地进行消毒，整个富集比斌每三个月。如果这是必要的，另一家大型货柜充实可用，设置其他富集容器在1.2节详述。和动物转移到新的容器中，而前一个被清洗。 </li></ol> 4.控制住房情况<ol><li>房子的动物的对照组中尺寸30.5厘米×19厘米×14厘米的微隔离器笼中。包括用于盛装食物和水的瓶子，如果笼不挂接到一个自动洒水系统在笼子里的电线架。 </li><li>提供相同的玉米芯被褥在控制笼在EE。为4cm的×4厘米的nestlet的老鼠做窝出来。 </li><li>更换和/或清洁笼子，喂养一周一次的电线，食物和水。通过笼洗干净的笼子和铁丝衣架或第1.1.1.1尽可能详细。更加频繁地清洗鸡笼，如果动物小便比较频繁，或者如果饮用水泄漏到床上用品。 </li><li>监测控制住房日常动物的健康。保证动物有充足的食物和水。 </li><li>众议院3〜5只小鼠同性别的普通鼠笼的。不提供任何玩具，管，或在笼笼。 </li><li>机构实验动物护理设施的健康和实验室技术人员可以对这些控制老鼠提供饲养。 </li><li>饲养动物在12小时的光/暗周期作为对于小鼠中EE。 </li></ol>

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作者宣称没有利益冲突。

EE对基因表达的健壮效果在大脑中，降低肥胖和癌症生长在小鼠中在很大程度上取决于研究者的能力，以保持新的环境和处理的动物中促进身体活动，社交和认知挑战的方式，但没有痛苦的动物。有两个最重要的程序性步骤，记住。首先，记住每星期更改放置玩具，物件，和笼子的。尽管玩具和物体可能与前一周相同，老鼠感知环境的小说。更改玩具和对象本身具有不同的人每隔一周。其次，记得要保持环境清洁。如果弄脏被褥没有得到消除，增加的氮含量可以是一个压力源给动物。 此外，还有许多技术来注意到本EE协议。利用不同的或独特的玩具和不同塑料管的迷宫设计的鼓励。环境可以是具有挑战性的，但应不构成对动物的健康构成威胁。此外，要注意玩具的功能失调的，因为不正常的玩具增加鼠标肢体的风险被抓住，或者消耗咀嚼它可能是有毒的动物。一恒定的EE是使用三个飞碟车轮上圆顶的顶部，由2-3日志螯合到bin的一角或一侧。运行日志后面的碟子这样的设置一直存在于我们所有的铀浓缩研究。在其他对象的使用和放置而言，布局的以上描述是EE设置的基本蓝图。变异的塑料管这个基础框架，车轮跑，跑碟，网箱和日志应提供足够的新的环境，以重现报告的结果设置的。 如果与患有糖尿病或其他代谢转基因动物工作疾病，狠抓食品和水的消耗，以确保动物不会跑出来的食物和水。如果动物有糖尿病，他们会小便较多，因此EE壳体的被褥可能需要现场检查和清洁更频繁。在EE房屋需要拆除的床上用品最常见的地方是死角。记得调整车轮等玩具，让他们可以使用该动物。动物是能够运行飞碟轮进被褥和运行敲了车轮的。如果动物是年轻的，3到5周龄，他们可能挖下在EE的笼中，并在那里隐藏起来，使研究人员无能，其中动物。当拆除弄脏被褥，玩具更换或清洗笼子，建议把动物在一个干净整洁的标准笼，以免他们强调了在调整他们的环境。这是比较容易得到所有的动物在一个笼子里，如果他们有较少的地方，在ENV隐藏ironment。因此，之前封存的动物关在笼子里取出玩具，使过程更容易。此外，不要将超过5-6动物在一个单一的标准笼子在等待清洗或调整自己的EE环境。雄性动物EE可以是积极的特别是当EE在成年期开始。因此，观察其环境的任何受伤或死亡的动物是很重要的。 此外，动物的典型数目，我们的房子在EE集装箱的这种大尺寸为10-20只。动物的数量其他研究者使用EE而变化，使用约10或更少的小鼠，和笼或仓的尺寸应确定的动物的数量，以房子在EE时予以考虑。有太多的动物的生活环境会导致侵略雄性小鼠。我们住在EE老鼠一直是C57BL / 6背景。其它菌株的小鼠可以是更多或更少的攻击性，或更容易出现健康问题这个EE设置。这应该被考虑在确定为小鼠和富集的环境的饲养计划。 四周EE壳体足以诱导减少肥胖，降瘦素水平，并抑制B16黑色素瘤的生长。再EE会导致新陈代谢和抑制癌症的作用更强。如果小鼠中或暴露于EE之前经受外科手术，可以将它们安置与缝线完好无损。是否动物反应良好的这个特定EE设置与外科U形钉或导管完好尚未研究。此外，我们目前正在调查这个特殊的EE如何影响老年动物的寿命或长期保健。初步数据表明，雌性C57BL / 6小鼠中，10个月的年龄，响应于类似EE到年轻小鼠。在EE壳体的一个限制是容纳这样一个大容器在动物设施的空间，并优先地在一个性别特定房间。因此，未来的研究EFFEE的规模较小学分，以及发现玩具易清洗，忍受高温清洁和安全的动物健康，将改善的EE中代谢和癌症研究中的应用。

丰富环境（EE）是用来探索的复杂和具有挑战性的环境中，不强调动物1效果的实验范式。 EE是一个增加的空间，体力活动，和社会交往，这反过来又增加感觉，认知，运动和社会刺激2组成动物壳体技术。冰屋，运行轮子，轮子飞碟，管迷宫，和其他对象的居住环境推动这一感官认知，社会和运动刺激，促进勘探和互动。在外壳的变化的对象的布局经常提出了一种新的环境中，向其中将小鼠被迫适应。这种策略提供了诱导有益的，良性的，健康的适应性反应，称为良性压力，而不是更厌恶，恶劣的环境或适应不良的困扰3,4-温和和短暂的挑战。通过促进良性压力和限制有害困扰，老鼠展示各种有利表型。 EE是一个可靠的实验模型具有广泛的应用，而具有不会产生传统上认为是压力1元素。已经研究了超过半个世纪EE对啮齿动物的影响。在20世纪60年代早期的研究表明，皮质胆碱酯酶水平下降和皮层下胆碱酯酶水平在被安置在环境与增加的生活空间，大鼠的数量增加，以及各种木制玩具，迷宫和平台5,6-老鼠增加。此外，EE与在不同年龄和遗传背景的小鼠中的脑，行为和代谢许多适应性变化相关联。因此，EE是进行的实验研究对小鼠的环境的影响的范围广阔的有用的范例。 EE效果可以在小鼠中一样迅速被观察为一个星期曝光，并且可以在动物中作为旧被视为18个月7。 EE是经常ü在sed的神经科学和神经行为实验，研究恢复功能，学习和记忆2。此外，EE对各种毒素诱导和人类神经系统疾病的转基因动物模型，包括亨廷顿氏病，阿尔茨海默氏病，帕金森氏症，癫痫症，中风的表型相当大的影响，并且更2。 然而，多年来一直存在矛盾与来自不同实验室的艰苦学习的充实设计进行比较。例如，每对相对于上面提到的人类神经系统疾病的EE效果的研究已经变参数的富集。亨廷顿氏病的研究收纳4-6小鼠的大笼（44×28×12.5厘米3）含有纸箱，隧道，和片材，以及木，塑料对象被改变每两天8,9。一对老年性痴呆所做的研究＃8217; S在包含2转轮，塑料管，纸箱被改变或重新安排每周10的排料较大的笼（1米3）装20只。 EE的许多设置有类似的主题，例如上运行或隐藏的物体，但每EE外壳，生活区的小鼠的数目，和改变环境的周期变化不大。 EE的不一致的设计导致了电子工程效果失败的复制。我们对癌症和新陈代谢数据一起表明，在下面的详细EE壳体协议导致显著抗癌和抗肥胖效果14,15提供刺激的结合。然而，通过不同的实验室可能影响EE的结果，如被认为是在一个EE设置的差值未能尝试重现上的植入小鼠11特定癌症肿瘤的生长EE影响。的不同的结果可能是由于多种原因的范围往复米的肿瘤细胞培养物，以用于清洁房屋设备11洗涤剂的类型的不同的增长率。为了复制看到在我们的实验的结果，浓缩和畜牧业的特定设计是必需的。下面的过程详细介绍了EE住房，将允许其他研究人员成功地复制我们的有效富集模式。

<table><tbody><tr><td>Large enrichment bin (120 cm x 90 cm x 76 cm)</td><td>Custom made.</td><td>Custom made.</td><td>Made of polypropylene. Edges of the bin are 1.5 cm thick.</td></tr><tr><td>Large enrichment bin alternative (120 cm x 110 cm x 76 cm)</td><td>Global Industrial</td><td>155202</td><td>If necessary, this bin works as an alternative to the one above.</td></tr><tr><td>Habitrail Mini tubes</td><td>Habitrail</td><td>62720; 62705; 62725; 62715; 62054</td><td>-</td></tr><tr><td>Plastic igloos with saucer wheels</td><td>Bio Serv</td><td>K3327; K3250</td><td>-</td></tr><tr><td>Metal Running Wheels</td><td>Super Pet</td><td>61392; 61394; 61396</td><td>-</td></tr><tr><td>Manzanita Wood Gnawing Sticks, 3&quot;</td><td>Bio Serv</td><td>W0016</td><td></td></tr><tr><td>Mouse Tunnels</td><td>Bio Serv</td><td>K3322</td><td>-</td></tr><tr><td>Mouse cages that go in the large EE bin.</td><td>Lab Products Inc</td><td>10027 Mouse Cage</td><td>-</td></tr><tr><td>Cage Klenz 180 Alkaline Cage Wash Detergent, Cage Klenz 250 Acid Detergent</td><td>Steris Life Sciences</td><td>1K1802; 1K2502</td><td>These detergents are used in the cage wash for the toys, large enrichment bins, and cages.</td></tr><tr><td>Sporklenz</td><td>Steris Life Sciences</td><td>6526Q8</td><td>Alternative sporicide/disinfectant to washing toys, bins, and cages in cage wash.</td></tr><tr><td>Bed-O-Cobs 1/4&quot; bedding</td><td>The Andersons, Inc.</td><td>4B</td><td>Corn cob bedding is 1/4&quot; in diameter.</td></tr><tr><td>Nestlets for control housed mice</td><td>Ancare</td><td></td><td>Cotton squares</td></tr></tbody></table>

a protocol for housing mice in an enriched environment

Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent studies demonstrate that environmental enrichment decreases adiposity, increases energy expenditure, resists diet induced obesity, and causes cancer remission and inhibition in mice. EE typically consists of larger living space, a variety of &#8216;toys&#8217; to interact with, running wheels, and can include a number of other novel environmental changes. All of this fosters a more complex social engagement, cognitive and physical stimulations. Importantly, the toy location and type of toy is changed regularly, which encourages the mice to adapt to a frequently changing and novel environment. Many variables can be manipulated in EE to promote health effects in mice. Thus these approaches are difficult to control and must be properly managed to successfully replicate the associated phenotypes. Therefore, the goal of this video is to demonstrate how EE is properly set up and maintained to assure a complex, challenging, and controlled environment so that other researchers can easily reproduce the protective effects of EE against obesity and cancer.

EE影响生长因子的表达，增加了中枢神经系统（CNS）12,13内神经发生和细胞的存活。最近的研究已经表明，EE这种技术导致癌症生长的显着抑制在三个小鼠癌症模型包括B16黑色素瘤，MC38结肠癌和APC 分钟/ +小鼠包含种系突变和很容易受到自发腺瘤的形成肠子14。结果在图2中确认的B16黑色素瘤的肿瘤生长抑制植入暴露于EE 5周（〜减少肿瘤质量的80％）的小鼠。癌细胞生长抑制甚至在小鼠中观察到，当EE发起的肿瘤已经建立了14后。 EE造成了更大的抑制黑素瘤生长在高脂饮食诱导的肥胖小鼠（〜减少肿瘤质量的70％）相比，在正常体重（〜减少肿瘤质量的50％）14只小鼠。 EE IND<html> uced签名变化的血清生物标志物包括鲁棒降瘦素，减少的IGF-1，和脂联素水平14的上升。 此外，EE的这种技术减少肥胖，增加能量消耗，导致对饮食诱导的肥胖抗性，并诱导白色至棕色脂肪表型开关通过激活下丘脑- sympathoneural脂肪细胞轴线15。在肥胖的减少被认为是早期六天暴露于EE（ 图3A，B），并再次在动物暴露于EE四星期（ 图3C，D）的确认。同样重要的是要注意的是，一个，使用EE相关的抗癌和抗肥胖效果不能由体力活动记帐单，和，二，EE效果可以通过脑源性神经营养因子的过度表达被再现（BDNF ）下丘脑14,15。 <html> 2874fig1.jpg"/&gt; 图1:丰富环境仓建立的丰富环境有120厘米×90厘米面积包括两个修改笼，跑车轮，带轮子飞碟，塑料管材，木原木等塑料玩具富集冰屋。 <img alt="图2" src="/files/ftp_upload/52874/52874fig2.jpg" /> 图2:丰富环境降低了肿瘤的生长C57BL / 6雄性小鼠三周龄雄性小鼠的房子在电子工程或控制的笼子前，肿瘤接种5周。。 B16黑色素瘤肿瘤重量在每只动物皮下10 5个细胞的接种上述右胁17天后（每组n = 10组。学生t-检验 ，* P &lt;0.05）。 <img alt="图3a" src="/files/ftp_upload/52874/52874fig3a.jpg" /> <img alt="图3b" src="/files/ftp_upload/52874/52874fig3b.jpg" /> S / ftp_upload / 52874 / 52874fig3c.jpg"/&gt; <img alt="图3d" src="/files/ftp_upload/52874/52874fig3d.jpg" /> 图3:丰富环境减少肥胖的C57BL / 6雄性小鼠三周龄小鼠进行EE。一组6天，另四个星期。 （ 一 ）在EE六天减少脂肪垫的重量（N =每组5。学生的t检验 ，* P &lt;0.05）。 （ 二）在EE六天减少脂肪垫的重量相对于体重（N =每组5。学生的t检验 ，* P &lt;0.05）。 （C）四个星期下降EE脂肪垫的重量（N =每组5。学生的t检验 ，* P &lt;0.05）。 （D）四个星期下降EE脂肪垫的重量相对于体重（N =每组5。学生的t检验 ，* P &lt;0.05）。 BAT:棕色脂肪组织，IWAT:腹股沟白色脂肪组织，EWAT:附睾白色脂肪组织，RWAT:腹膜后脂肪组织。

Watch this Scientific Journal Video about A Protocol for Housing Mice in an Enriched Environment at JoVE.com

A Protocol for Housing Mice in an Enriched Environment

Environmental enrichment for mice requires a complex and challenging setup, as well as comprehensive husbandry and handling techniques to assure robust metabolic and anti-cancer effects in the mice. This protocol provides detailed procedures to reproduce the above mentioned effects in mice.

在丰富环境的协议房屋小鼠

Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent ...

a-protocol-for-housing-mice-in-an-enriched-environment

Nanyang Technological University

Research

JoVE Journal

Behavior

18.2K 次观看.  The Ohio State University. Environmental enrichment for mice requires a complex and challenging setup, as well as comprehensive husbandry and handling techniques to assure robust metabolic and anti-cancer effects in the mice. This protocol provides detailed procedures to reproduce the above mentioned effects in mice.

视频: A Protocol for Housing Mice in an Enriched Environment

The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment

Environmental enrichment can dramatically influence the development and function of neural circuits. Further, enrichment has been shown to successfully delay the onset of symptoms in models of Huntington&#8217;s disease 1-4, suggesting environmental factors can evoke a neuroprotective effect against the progressive, cellular level damage observed in neurodegenerative disorders. The ways in which an animal can be environmentally enriched, however, can vary considerably. Further, there is no straightforward manner in which the effects of environmental enrichment can be assessed: most methods require either fairly complicated behavioral paradigms and/or postmortem anatomical/physiological analyses. This protocol describes the use of a simple and inexpensive behavioral assay, the Puzzle Box 5-7 as a robust means of determining the efficacy of increased social, sensory and motor stimulation on mice compared to cohorts raised in standard laboratory conditions. This simple problem solving task takes advantage of a rodent&#8217;s innate desire to avoid open enclosures by seeking shelter. Cognitive ability is assessed by adding increasingly complex impediments to the shelter&#8217;s entrance. The time a given subject takes to successfully remove the obstructions and enter the shelter serves as the primary metric for task performance. This method could provide a reliable means of rapidly assessing the efficacy of different enrichment protocols on cognitive function, thus paving the way for systematically determining the role specific environmental factors play in delaying the onset of neurodevelopmental and neurodegenerative disease.

Environmental enrichment provides a potential protective effect against neurodegenerative disorders. Currently, however, there is no easy way of determining the efficacy of enrichment procedures. This protocol describes a simple &#8220;Puzzle Box&#8221; method for assessing an animal&#8217;s cognitive function, in order to reveal the effectiveness of environmental enrichment.

该拼图方块的使用作为评价环境富集的功效的一种手段

Environmental enrichment can dramatically influence the development and function of neural circuits.  Further, enrichment has been shown to successfully ...

科研

行为学

A Method to Define the Effects of Environmental Enrichment on Colon Microbiome Biodiversity in a Mouse Colon Tumor Model

Several recent studies have illustrated the beneficial effects of living in an enriched environment on improving human disease. In mice, environmental enrichment (EE) reduces tumorigenesis by activating the mouse immune system, or affects tumor bearing animal survival by stimulating the wound repair response, including improved microbiome diversity, in the tumor microenvironment. Provided here is a detailed procedure to assess the effects of environmental enrichment on the biodiversity of the microbiome in a mouse colon tumor model. Precautions regarding animal breeding and considerations for animal genotype and mouse colony integration are described, all of which ultimately affect microbial biodiversity. Heeding these precautions may allow more uniform microbiome transmission, and consequently will alleviate non-treatment dependent effects that can confound study findings. Further, in this procedure, microbiota changes are characterized using 16S rDNA sequencing of DNA isolated from stool collected from the distal colon following long-term environmental enrichment. Gut microbiota imbalance is associated with the pathogenesis of inflammatory bowel disease and colon cancer, but also of obesity and diabetes among others. Importantly, this protocol for EE and microbiome analysis can be utilized to study the role of microbiome pathogenesis across a variety of diseases where robust mouse models exist that can recapitulate human disease.

Environmental Enrichment (EE) is an animal housing environment that is used to reveal mechanisms that underlie the connections between lifestyle, stress, and disease. This protocol describes a procedure that uses a mouse model of colon tumorigenesis and EE to specifically define alterations in microbiota biodiversity that may impact animal mortality.

一种确定环境富集对小鼠结肠肿瘤模型结肠菌群生物多样性影响的方法

Several recent studies have illustrated the beneficial effects of living in an enriched environment on improving human disease. In mice, environmental ...

癌症研究

Assessing Burrowing, Nest Construction, and Hoarding in Mice

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening of possible treatments for AD currently largely focuses on cognitive testing, which frequently demands expensive equipment and lots of experimenter time. However, human episodic memory (the most severely affected aspect of memory in AD) is different to rodent memory, which seems to be largely non-episodic. Therefore the present ways of screening for new AD treatments for AD in rodents are intrinsically unlikely to succeed. A new approach to preclinical screening would be to characterise the ADL of mice. Fortuitously, several such assays have recently been developed at Oxford, and here the three most sensitive and well-characterised are presented.
Burrowing was first developed in Oxford13. It evolved from a need to develop a mouse hoarding paradigm. Most published rodent hoarding paradigms required a distant food source to be linked to the home cage by a connecting passage. This would involve modifying the home cage as well as making a mouse-proof connecting passage and food source. So it was considered whether it would be possible to put the food source inside the cage. It was found that if a container was placed on the floor it was emptied by the next morning., The food pellets were, however, simply deposited in a heap at the container entrance, rather than placed in a discrete place away from the container, as might be expected if the mice were truly hoarding them. Close inspection showed that the mice were performing digging ("burrowing") movements, not carrying the pellets in their mouths to a selected place as they would if truly hoarding them.6



Food pellets are not an essential substrate for burrowing; mice will empty tubes filled with sand, gravel, even soiled bedding from their own cage. Moreover, they will empty a full tube even if an empty one is placed next to it8.



Several nesting protocols exist in the literature. The present Oxford one simplifies the procedure and has a well-defined scoring system for nest quality5. 



A hoarding paradigm was later developed in which the mice, rather than hoarding back to the real home cage, were adapted to living in the "home base" of a hoarding apparatus. This home base was connected to a tube made of wire mesh, the distal end of which contained the food source. This arrangement proved to yield good hoarding behaviour, as long as the mice were adapted to living in the "home base" during the day and only allowed to enter the hoarding tube at night.

Burrowing, nesting, and hoarding are species-typical activities that mice readily perform in the laboratory. This article describes how they can be easily and cheaply assessed. These protocols are extremely sensitive to mouse strain, brain lesions and diseases. Moreover they constitute &#x201C;environmental enrichment&#x201D; for the mice, and embody the &#x201C;Refinement&#x201D; aspect of the &#x201C;3 Rs&#x201D;18.

评估挖洞，在小鼠的鸟巢建设和囤积

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening ...

神经科学

Nest Building Behavior as an Early Indicator of Behavioral Deficits in Mice

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents synthetic and/or natural materials (such as twine, tissue, cotton, paper, and hay) as a gauge of their overall well-being and as an ancillary assessment to predict the possible decline in cognition. Typically, changes in nesting behaviors, such as failure to create a nest, indicate a change in health or welfare. In addition, nesting behavior is sensitive to many environmental and physiological challenges, as well as many genetic mutations underlying pathological disease states. The following protocol describes a nesting behavior paradigm that explores the usage of four types of nesting material. In addition, the protocol utilizes intraclass correlations to demonstrate that inter-rater reliability is higher when nests are constructed out of shredded paper compared to other common nesting materials such as cotton squares, paper twists, and soft cob bedding. The chosen methodology and statistical considerations (i.e., intraclass correlation) for this assay may be of interest for those conducting experiments assessing the quality of living of mice.&#160;

Here, we present a protocol to quantify nest building behavior in mice, which is known to be impaired in several neurological disorders and diseases. This protocol examines the utility of four materials and offers the opportunity to quantify the rater agreement in scoring, improving the validity and reliability of the assay.

巢穴建筑行为作为小鼠行为缺陷的早期指标

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents ...

Assessment of Mouse Judgment Bias through an Olfactory Digging Task

Judgment biases (JB) are differences in the way that individuals in positive and negative affective/emotional states interpret ambiguous information. This phenomenon has long been observed in humans, with individuals in positive states responding to ambiguity 'optimistically' and those in negative states instead showing 'pessimism'. Researchers aiming to assess animal affect have taken advantage of these differential responses, developing tasks to assess judgment bias as an indicator of affective state. These tasks are becoming increasingly popular across diverse species and fields of research. However, for laboratory mice, the most widely used vertebrates in research and a species heavily relied upon to model affective disorders, only one JB task has been successfully validated as sensitive to changes in affective state. Here, we provide a detailed description of this novel murine JB task, and evidence of its sensitivity to mouse affect. Though refinements are still necessary, assessment of mouse JB opens the door for answering both practical questions regarding mouse welfare, and fundamental questions about the impact of affective state in translational research.

This article provides a detailed description of a novel mouse judgment bias protocol. Evidence of this olfactory digging task's sensitivity to affective state is also demonstrated and its utility across diverse research fields is discussed.

通过嗅觉挖掘任务评估小鼠判断偏差

Judgment biases (JB) are differences in the way that individuals in positive and negative affective/emotional states interpret ambiguous information. This ...

Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice

Long-lasting changes in the brain or &#8216;brain plasticity&#8217; underlie adaptive behavior and brain repair following disease or injury. Furthermore, interactions with our environment can induce brain plasticity. Increasingly, research is trying to identify which environments stimulate brain plasticity beneficial for treating brain and behavioral disorders. Two environmental manipulations are described which increase or decrease the number of tyrosine hydroxylase immunopositive (TH+, the rate-limiting enzyme in dopamine (DA) synthesis) neurons in the adult mouse midbrain. The first comprises pairing male and female mice together continuously for 1 week, which increases midbrain TH+ neurons by approximately 12% in males, but decreases midbrain TH+ neurons by approximately 12% in females. The second comprises housing mice continuously for 2 weeks in &#8216;enriched environments&#8217; (EE) containing running wheels, toys, ropes, nesting material, etc., which increases midbrain TH+ neurons by approximately 14% in males. Additionally, a protocol is described for concurrently infusing drugs directly into the midbrain during these environmental manipulations to help identify mechanisms underlying environmentally-induced brain plasticity. For example, EE-induction of more midbrain TH+ neurons is abolished by concurrent blockade of synaptic input onto midbrain neurons. Together, these data indicate that information about the environment is relayed via synaptic input to midbrain neurons to switch on or off expression of &#8216;DA&#8217; genes. Thus, appropriate environmental stimulation, or drug targeting of the underlying mechanisms, might be helpful for treating brain and behavioral disorders associated with imbalances in midbrain DA (e.g. Parkinson&#8217;s disease, attention deficit and hyperactivity disorder, schizophrenia, and drug addiction).

This protocol describes two different environmental manipulations and a concurrent brain infusion protocol to study environmentally-induced brain changes underlying adaptive behavior and brain repair in adult mice.

中脑多巴胺神经元的数目在成年小鼠环境的调变

Long-lasting changes in the brain or &#8216;brain plasticity&#8217; underlie adaptive behavior and brain repair following disease or injury. Furthermore, ...

<meta charset="utf8"></head><body>小鼠模型中自闭症谱系障碍的行为检测

Strategies for Assessing Autistic-Like Behaviors in Mice

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social communication impairments and restrictive or repetitive behaviors, such as hand flapping or lining up objects. These behavioral patterns can be reliably observed in mouse models with ASD-linked genetic mutations, making them highly useful tools for studying the underlying cellular and molecular mechanisms in ASD. Understanding how genetic changes affect the neurobiology and behaviors observed in ASD will facilitate the development of novel targeted therapeutic compounds to ameliorate core behavioral impairments. Our lab has employed several protocols encompassing well-described training and testing procedures that reflect a wide range of behavioral deficits related to ASD. Here, we detail two assays to study the core features of ASD in mouse models: self-grooming (a measure of repetitive behavior) and the three-chamber social interaction test (a measure of social interaction approach and preference for social novelty).

<meta charset="utf8"></head><body>评估小鼠自闭症样行为的策略

Rodent models are valuable tools for studying core behaviors related to autism spectrum disorder (ASD). In this article, we expound on two behavioral tests for modeling the core features of ASD in mice: self-grooming, which assesses repetitive behavior, and the three-chamber social interaction test, which documents social impairments.

评估小鼠自闭症样行为的策略

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social ...

Social Isolation Model: A Noninvasive Rodent Model of Stress and Anxiety

Anxiety disorders are one of the leading causes of disability in the United States (US). Current treatments are not always effective and less than 50% of patients achieve full remission. A critical step in developing a novel anxiolytic is to develop and utilize an animal model, such as mice, to study pathological changes and test drug target(s), efficacy, and safety. Current approaches include genetic manipulation, chronic administration of anxiety-inducing molecules, or the administration of environmental stress. These methods, however, may not realistically reflect anxiety induced throughout daily life. This protocol describes a novel anxiety model, which mimics the intentional or unintentional patterns of social isolation in modern life. The social isolation-induced anxiety model minimizes perceived distractions and invasiveness and utilizes wild type C57BL/6 mice. In this protocol, 6- to 8-week-old mice (male and female) are singly housed in opaque cages to visually block the external environment, such as neighboring mice, for 4 weeks. No environmental enrichments (such as toys) are provided, bedding material is reduced by 50%, any treatment of drug is administered as an agar form, and the exposure/handling of the mice is minimized. Socially isolated mice generated using this protocol exhibit greater anxiety-like behavior, aggression,&#160;as well as decreased cognition.

Presented here is a social isolation (SI)-induced anxiety mouse model that utilizes wild type C56BL/6J mice to induce stress and anxiety-like behavior with minimal handling and no invasive procedures. This model reflects modern life patterns of social isolation and is ideal for studying anxiety and related disorders.

社会隔离模型:压力和焦虑的非侵入性啮齿动物模型

Anxiety disorders are one of the leading causes of disability in the United States (US). Current treatments are not always effective and less than 50% of ...

在丰富环境的协议房屋小鼠

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评估小鼠自闭症样行为的策略

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评估小鼠自闭症样行为的策略

社会隔离模型:压力和焦虑的非侵入性啮齿动物模型