The Serial Anesthesia Array for the High-Throughput Investigation of Volatile Agents Using Drosophila melanogaster.
The Serial Anesthesia Array for the High-Throughput Investigation of Volatile Agents Using Drosophila melanogaster.
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DOI：
10.3791/65144
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发表时间：
2023-02-24
期刊：
影响因子：
--
通讯作者：
Perouansky M
中科院分区：
文献类型：
--
作者：
Olufs ZPG;Johnson-Schlitz D;Wassarman DA;Perouansky M
挥发性全身麻醉剂（VGAs）在世界范围内用于各种年龄和医疗条件的数百万人。高浓度的VGAs（数百微摩尔到低毫摩尔）是实现对大脑功能的深刻和非生理性抑制所必需的，对观察者来说，这就像“麻醉”一样。由如此高浓度的亲脂剂引发的全套附带效应尚不清楚，但已注意到与免疫-炎症系统的相互作用，尽管其生物学意义尚不清楚。为了研究VGAs在动物体内的生物学效应，我们利用果蝇提供的实验优势，开发了一种称为连续麻醉阵列（SAA）的系统。SAA由八个腔室组成，并串联到一个共同的流入。有些部件可在实验室获得，而其他部件可以很容易地制造或购买。汽化器，这是必要的VGAs的校准管理，是唯一的商业制造的组件。在运行期间，VGAs仅占流经SAA的大气的一小部分，因为大部分（通常超过95%）是载气；默认的载体是航空。然而，氧气和任何其他气体都可以被研究。与先前的系统相比，SAA的主要优势在于它允许多组苍蝇同时暴露于精确可滴定剂量的VGAs。在所有腔室中，几分钟内就能达到相同的VGAs浓度，从而提供无法区分的实验条件。每个房间可以容纳一只苍蝇到数百只苍蝇。例如，SAA可以同时检测八种不同的基因型或四种具有不同生物学变量的基因型（例如，男性与女性，老年与年轻）。我们使用SAA在两种与神经炎症-线粒体突变体和创伤性脑损伤（TBI）相关的实验苍蝇模型中研究了VGAs的药效学及其药理学相互作用。
Volatile general anesthetics (VGAs) are used worldwide on millions of people of all ages and medical conditions. High concentrations of VGAs (hundreds of micromolar to low millimolar) are necessary to achieve a profound and unphysiological suppression of brain function presenting as “anesthesia” to the observer. The full spectrum of the collateral effects triggered by such high concentrations of lipophilic agents is not known, but interactions with the immune-inflammatory system have been noted, although their biological significance is not understood. To investigate the biological effects of VGAs in animals, we developed a system termed the serial anesthesia array (SAA) to exploit the experimental advantages offered by the fruit fly (Drosophila melanogaster). The SAA consists of eight chambers arranged in series and connected to a common inflow. Some parts are available in the lab, and others can be easily fabricated or purchased. A vaporizer, which is necessary for the calibrated administration of VGAs, is the only commercially manufactured component. VGAs constitute only a small percentage of the atmosphere flowing through the SAA during operation, as the bulk (typically over 95%) is carrier gas; the default carrier is air. However, oxygen and any other gases can be investigated. The SAA’s principal advantage over prior systems is that it allows the simultaneous exposure of multiple cohorts of flies to exactly titrable doses of VGAs. Identical concentrations of VGAs are achieved within minutes in all the chambers, thus providing indistinguishable experimental conditions. Each chamber can contain from a single fly to hundreds of flies. For example, the SAA can simultaneously examine eight different genotypes or four genotypes with different biological variables (e.g., male vs. female, old vs. young). We have used the SAA to investigate the pharmacodynamics of VGAs and their pharmacogenetic interactions in two experimental fly models associated with neuroinflammation-mitochondrial mutants and traumatic brain injury (TBI).
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影响因子：
4.6
作者：
Olufs, Zachariah P. G.;Loewen, Carin A.;Perouansky, Misha
通讯作者：
Perouansky, Misha
影响因子：
2.9
作者：
Rand, Matthew D.
通讯作者：
Rand, Matthew D.
影响因子：
3.3
作者：
McGurk, Leeanne;Berson, Amit;Bonini, Nancy M.
通讯作者：
Bonini, Nancy M.
影响因子：
8.8
作者：
Olufs, Zachariah P. G.;Ganetzky, Barry;Perouansky, Misha
通讯作者：
Perouansky, Misha
影响因子：
8.8
作者：
Perouansky, Misha;Hentschke, Harald;Pearce, Robert A.
通讯作者：
Pearce, Robert A.