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Abstract：
Sound sensitivity is one of the most common sensory complaints for people with autism spectrum disorders (ASDs). How and why sounds are perceived as overwhelming by affected people is unknown. To process sound information properly, the brain requires high activity and fast processing, as seen in areas like the medial nucleus of the trapezoid body (MNTB) of the auditory brainstem. Recent work has shown dysfunction in mitochondria, which are the primary source of energy in cells, in a genetic model of ASD, Fragile X syndrome (FXS). Whether mitochondrial functions are also altered in sound-processing neurons, has not been characterized yet. To address this question, we imaged the MNTB in a mouse model of FXS. We stained MNTB brain slices from wild-type and FXS mice with two mitochondrial markers, TOMM20 and PMPCB, located on the Outer Mitochondrial Membrane and in the matrix, respectively. These markers allow exploration of mitochondrial subcompartments. Our integrated imaging pipeline reveals significant sex-specific differences between genotypes. Colocalization analyses between TOMM20 and PMPCB reveal that the integrity of mitochondrial subcompartments is most disrupted in female FXS mice compared to female wildtype mice. We highlight a quantitative fluorescence microscopy pipeline to monitor mitochondrial functions in the MNTB from control or FXS mice and provide four complementary readouts. Our approach paves the way to understanding how cellular mechanisms important to sound encoding are altered in ASDs.
摘要：
声音敏感性是自闭症谱系障碍（ASDs）患者最常见的感觉不适之一。如何以及为什么声音被受影响的人认为是压倒性的是未知的。为了正确处理声音信息，大脑需要高度的活动和快速的处理，在听觉脑干梯形体（MNTB）的内侧核等区域可见。最近的工作表明线粒体功能障碍，它们是细胞中能量的主要来源，在ASD的遗传模型中，脆性X综合征（FXS）。声音处理神经元的线粒体功能是否也发生了改变，还没有被定性。为了解决这个问题，我们在FXS的小鼠模型中成像了MNTB。我们用两种线粒体标记对野生型和FXS小鼠的MNTB脑切片进行染色，TOMM20和PMPCB,位于线粒体外膜和基质中，分别。这些标记允许探索线粒体亚区室。我们的整合成像管道揭示了FXS中线粒体长度程度的显着性别特异性差异。雄性FXS小鼠的线粒体总数也存在显着差异，然而,TOMM20和PMPCB之间的共定位分析表明，这些区室的完整性在雌性FXS小鼠中被破坏最多。我们强调了定量荧光显微镜管道，以监测来自对照或FXS小鼠的MNTB中的线粒体功能，并提供四个互补读数。我们的方法为理解ASD中对声音编码重要的细胞机制如何改变铺平了道路。
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■MNTB的线粒体结构存在性别差异。FXS雌性小鼠具有无序的线粒体,其也比野生型雌性更长并且分支更少。与雄性相比,雄性FXS小鼠具有更少的整体线粒体。
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■MNTB的线粒体结构存在性别差异。FXS雌性小鼠具有无序的线粒体,其也比野生型雌性更长并且分支更少。与雄性相比,雄性FXS小鼠具有更少的整体线粒体。
