Name: a novel method to model chronic traumatic encephalopathy in drosophila
Uploaded: 2017-07-04T13:00:00
Description: Watch this Scientific Journal Video about A Novel Method to Model Chronic Traumatic Encephalopathy in Drosophila at JoVE.com

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打击装置装配（ 图1 ） <ol><li>从1 mL结核菌素注射器中取出柱塞。切成1毫升标记的桶。 </li><li>从200μL移液器吸头上取下气溶胶屏障（直径3mm，直径4 mm），并将其用作冲击器。将冲击器放在注射器筒内。轻轻敲击枪管将冲击器移动到前端，平面覆盖喷嘴开口。 </li><li>将枪管末端连接到连接到果蝇麻醉站的二氧化碳（CO 2 ）流量调节器的塑料管上。 </li><li>将桶?...

<ol>
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忠实地建模CTE特征的动物模型，包括神经生理学改变，神经病理学特征和神经行为缺陷，对于揭示疾病机制和开发诊断和治疗目标至关重要。可以理解，人类疾病的动物模型在模拟所有临床相关终点方面是完美的。然而，我们认为，强大的CTE模型应该满足以下三个要求：（1）影响必须直接适用于具有完整的头皮和颅骨保护的头部; （2）在冲击暴露期间头部不应固定，以便允许快速加速 - 减速和旋...

慢性创伤性脑病（CTE）最近被认为是一种独特的神经变性疾病，与其他tau病，如阿尔茨海默病1分离 。与阿尔茨海默病和其他常见的tau蛋白病（其最重要的危险因素是年龄增长和痴呆家族史）不同，CTE如其名称所示，意味着与脑外伤历史密切相关，很可能与体育运动员接触，例如拳击手和足球运动员，以及2,3,4,5的退伍军人。它被认为是通过反复的震荡和冲击打击脑袋。患者可能会出现症状和体征，如认知缺陷，情绪和行为变化以及运动功能障碍，其与阿尔茨海默病，额颞叶痴呆，路易体痴呆和帕金森病6 。相比之下，脑组织的死后检查显示在皮层sulci深度周围的小血管周围的超磷酸化tau积累的不同模式，在其他退化病症中未观察到的病理特征7 。然而，到目前为止，关于导致疾病表现的发病机制知之甚少。这在很大程度上是由于缺乏一个忠实的动物模型 - 只是最近才有了5,8的鼠类模型。这些模型生物体具有成本密集型护理和相对较长使用寿命的缺点，不太适用于神经退行性疾病研究。 与哺乳动物相比，无脊椎动物如果蝇是一种很好的替代方案，具有成本效益的维护，广泛的解剖遗传决定因素的工具，寿命相对较短9 。值得注意的是，飞行和人类大脑分享进化上保守的分子和细胞通路，以及解剖学相似性10,11,12 。已经报道了两个巧妙的果蝇模型来研究创伤性脑损伤。由Katzenberger及其同事设计的第一个“高冲击创伤”（HIT）装置将塑料瓶中的自由移动的苍蝇与金属弹簧13,15的自由端相连。当塑料小瓶倾斜直立并释放时，它会撞到聚氨酯垫，并在苍蝇弹到小瓶壁并反弹时给野生动物施加创伤。相比之下，Barekat和同事们设计了一种不同的送货方式使用Omni Bead Ruptor-24匀浆机平台14 。苍蝇与CO 2失活，并置于2mL螺旋管中，将其固定在均化器上并进行预编程的摇动条件。使用组织匀浆器系统的一个好处是，实验者可以调节受伤的强度，受伤持续时间和伤害发作次数。然而，这两个制度都有同样的缺点：头部的主要伤害在冲击位置和强度方面是随机的。此外，这两种方法导致相当大的死亡率，这是由身体和内脏其他部位的不可避免的附带损害造成的。在这里，我们描述了一种在果蝇中诱导mTBI的新方法。我们的装置由气体推进的弹道冲击器组成。与现有的果蝇模型14,15相比，我们的方法具有独特的优势可引起影响，仅针对自由移动的飞头，从而允许准确控制各种因素，如影响严重性，影响之间的时间间隔以及持续影响的总数。

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			<td height="20" style="height:20px;width:216px;">Aerosol Barrier</td>
			<td style="width:151px;">USA Scientific</td>
			<td style="width:119px;">1120-8810</td>
			<td style="width:207px;">Used as an impactor</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">200 ul Pipette Tip</td>
			<td style="width:151px;">USA Scientific</td>
			<td style="width:119px;">1111-0706</td>
			<td>Used as a fly head holder</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">1000 ul Pipette Tip</td>
			<td style="width:151px;">USA Scientific</td>
			<td style="width:119px;">1122-1830</td>
			<td>Used as a connector</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">1 ml Tuberculin Syringe</td>
			<td style="width:151px;">Becton Dickinson</td>
			<td style="width:119px;">309625</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">60 mm Petri Dishes</td>
			<td style="width:151px;">Fisher Scientific</td>
			<td>FB0875713A</td>
			<td>Used as a tracking arenas</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">Flow Regulator</td>
			<td>Genesee Scientific</td>
			<td style="width:119px;">59-122WC</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">Standard Clamp Holder/stand</td>
			<td style="width:151px;">EISCO Scientific</td>
			<td style="width:119px;">CH0688</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">Fine Brush</td>
			<td style="width:151px;">Genesee Scientific</td>
			<td style="width:119px;">59-204</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">Flypad</td>
			<td style="width:151px;">Genesee Scientific</td>
			<td style="width:119px;">59-114</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">Sylgard Silicone Elastomer</td>
			<td style="width:151px;">Dow Corning</td>
			<td>4019862</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">CCD Camera</td>
			<td style="width:151px;">Microsoft&#160;</td>
			<td style="width:119px;">HD-5000</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Ctrax Walking Fly Tracker</td>
			<td style="width:151px;">Caltech</td>
			<td style="width:119px;">Ctrax 0.2.11</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">MATLAB Image Processing Toolbox</td>
			<td style="width:151px;">MATLAB</td>
			<td style="width:119px;">R2015b</td>
			<td></td>
		</tr>
	</tbody>
</table>

a novel method to model chronic traumatic encephalopathy in drosophila

慢性创伤性脑病（CTE）是一种既定的神经退行性疾病，与暴露于重度轻度创伤性脑损伤（mTBI）密切相关。尽管最近有一个界定神经病理学标准的共识，但其复杂的病理变化的机制仍然很难捉摸。在这里，我们描述了一种在黑腹果蝇 （ 果蝇 ）中开发CTE模型的新方法，旨在鉴定导致大脑中特征性过度磷酸化tau积累和神经元死亡的关键基因和途径。对可能受到轻微封闭伤害的强度影响直接传递给飞头，使头部快速加速和减速。我们的方法消除了其他果蝇 mTBI模型固有的潜在问题（ 例如，动物死亡可能是由于损伤引起的身体其他部位或内脏）。较少的劳动力和成本密集的动物护理，短寿命和广泛的遗传工具使果蝇成为研究CTE发病机理的理想选择，并且可以进行大规模，全基因组的前期遗传和药理筛选。我们预计，模型的持续表征将为疾病预防和治疗方法产生重要的机械观点。

为了建立使用成年果蝇的CTE模型，我们确定了我们的装置在单次闭合性头部受伤时的有效性。为了消除与基因型，性别或年龄有关的变化，我们在实验中使用了2日龄的Canton-S WT雌性苍蝇。通过在100 kPa的恒定气压下调节CO 2的流量，可以很容易地控制冲击器的强度。以最高流速（15L / min）暴露于单次冲击的苍蝇显示出最小的外部缺陷（ 图2</stron...

Watch this Scientific Journal Video about A Novel Method to Model Chronic Traumatic Encephalopathy in Drosophila at JoVE.com

A Novel Method to Model Chronic Traumatic Encephalopathy in Drosophila

在这里，我们描述了一种在黑腹果蝇中引起封闭头部创伤性脑损伤的新方法。我们的方法的优点是可以直接将可重复的冲击强度提供给头部。无脊椎动物系统的进一步探索将有助于阐明慢性创伤性脑病的发病机制。

慢性创伤性脑病模型的一种新方法<em&gt;果蝇</em

Chronic Traumatic Encephalopathy (CTE) is an established neurodegenerative disease that is closely associated with exposure to repetitive mild Traumatic ...

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A Novel Method to Model Chronic Traumatic Encephalopathy in Drosophila

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A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila

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Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies ...

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Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral ...

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Multichannel electrode arrays offer insight into the working brain and serve to elucidate neural processes at the single-cell and circuit levels. ...