Rotschafer Sarah E, Marshak Sonya, Cramer Karina S
Department of Neurobiology and Behavior, University of California Irvine, Irvine, California, 92697, United States of America.
PLoS One. 2015 Feb 13;10(2):e0117266. doi: 10.1371/journal.pone.0117266. eCollection 2015.
Fragile X Syndrome (FXS), a neurodevelopmental disorder, is the most prevalent single-gene cause of autism spectrum disorder. Autism has been associated with impaired auditory processing, abnormalities in the auditory brainstem response (ABR), and reduced cell number and size in the auditory brainstem nuclei. FXS is characterized by elevated cortical responses to sound stimuli, with some evidence for aberrant ABRs. Here, we assessed ABRs and auditory brainstem anatomy in Fmr1-/- mice, an animal model of FXS. We found that Fmr1-/- mice showed elevated response thresholds to both click and tone stimuli. Amplitudes of ABR responses were reduced in Fmr1-/- mice for early peaks of the ABR. The growth of the peak I response with sound intensity was less steep in mutants that in wild type mice. In contrast, amplitudes and response growth in peaks IV and V did not differ between these groups. We did not observe differences in peak latencies or in interpeak latencies. Cell size was reduced in Fmr1-/- mice in the ventral cochlear nucleus (VCN) and in the medial nucleus of the trapezoid body (MNTB). We quantified levels of inhibitory and excitatory synaptic inputs in these nuclei using markers for presynaptic proteins. We measured VGAT and VGLUT immunolabeling in VCN, MNTB, and the lateral superior olive (LSO). VGAT expression in MNTB was significantly greater in the Fmr1-/- mouse than in wild type mice. Together, these observations demonstrate that FXS affects peripheral and central aspects of hearing and alters the balance of excitation and inhibition in the auditory brainstem.
脆性X综合征（FXS）是一种神经发育障碍，是自闭症谱系障碍最常见的单基因病因。自闭症与听觉处理受损、听觉脑干反应（ABR）异常以及听觉脑干核细胞数量和大小减少有关。FXS的特征是对声音刺激的皮层反应增强，有一些证据表明ABR异常。在这里，我们评估了FXS动物模型Fmr1-/-小鼠的ABR和听觉脑干解剖结构。我们发现Fmr1-/-小鼠对点击声和纯音刺激的反应阈值升高。Fmr1-/-小鼠ABR早期波峰的反应幅度降低。与野生型小鼠相比，突变体中I波峰反应随声音强度的增长不那么陡峭。相比之下，IV波峰和V波峰的幅度和反应增长在这些组之间没有差异。我们没有观察到波峰潜伏期或峰间潜伏期的差异。Fmr1-/-小鼠的腹侧耳蜗核（VCN）和梯形体内侧核（MNTB）中的细胞大小减小。我们使用突触前蛋白标记物量化了这些核中抑制性和兴奋性突触输入的水平。我们测量了VCN、MNTB和外侧上橄榄核（LSO）中的VGAT和VGLUT免疫标记。Fmr1-/-小鼠MNTB中的VGAT表达明显高于野生型小鼠。总之，这些观察结果表明，FXS会影响听力的外周和中枢方面，并改变听觉脑干中兴奋和抑制的平衡。
