Department of Otorhinolaryngology Head and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China (mainland).
Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Laboratory of Brain Disorders (Ministry of Science and Technology), Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China (mainland).
Med Sci Monit. 2018 Jan 20;24:397-404. doi: 10.12659/msm.908432.
BACKGROUND Congenital single-side deafness (SSD) affects sound localization even after cochlear implantation (CI) in some conditions. The medial nucleus of the trapezoid body (MNTB) plays an important role in binaural benefit and sound localization, but little is known about intrinsic molecular changes in MNTB with SSD. We aimed to observe changes in MNTB in early-developmental SSD rats, including the key neurotransmitters (GABA, Gly, Glu) and major receptors (GABAa-R/GABAb-R for GABA, Gly-R for Gly, and AMPA/NMDA for Glu). MATERIAL AND METHODS The model of early-developmental SSD was acquired by right cochlear ablation at P12 and confirmed by ABR. High-performance liquid chromatography fluorescence detection (HPLC-FLD) was performed to measure the levels of neurotransmitters in MNTB. The relative expression of neurotransmitter receptors was tested by quantitative real-time PCR analysis. RESULTS (1) The right MNTB of experimental rats had an increase in GABA, Gly, and Glu at 4 weeks after right cochlear ablation (P<0.05). (2) At 2 weeks, the left MNTB of experimental rats showed increases in GABAa-R, GABAb-R, Gly-R, and AMPA, while the right MNTB showed lower expression of NMDA (P<0.05). The higher receptors in left MNTB decreased to a level at which we found no difference at 1 week for GABAa-R and GABAb-R (P>0.05), and was even reversed for Gly-R and AMPA (P<0.05). (3) Gly level was significantly increased at 2 weeks bilaterally and continued to 4 weeks in the left MNTB (P<0.05). CONCLUSIONS Early-developmental SSD can lead to asymmetric distribution of neurotransmitters and receptors in MNTB, which can be the fundamental cause of defective sound localization after cochlear implantation.
在某些情况下,先天性单侧聋(SSD)即使在植入人工耳蜗(CI)后也会影响声音定位。梯形束内侧核(MNTB)在双耳获益和声音定位中发挥重要作用,但对于 SSD 中 MNTB 的内在分子变化知之甚少。我们旨在观察早期发育性 SSD 大鼠 MNTB 的变化,包括关键神经递质(GABA、Gly、Glu)和主要受体(GABAa-R/GABAb-R 用于 GABA、Gly-R 用于 Gly 和 AMPA/NMDA 用于 Glu)。
通过 P12 时右耳蜗消融建立早期发育性 SSD 模型,并通过 ABR 进行确认。采用高效液相色谱荧光检测(HPLC-FLD)测定 MNTB 中神经递质水平。通过定量实时 PCR 分析测试神经递质受体的相对表达。
(1)右耳蜗消融后 4 周,实验大鼠右 MNTB 中 GABA、Gly 和 Glu 增加(P<0.05)。(2)在 2 周时,实验大鼠左 MNTB 中 GABAa-R、GABAb-R、Gly-R 和 AMPA 增加,而右 MNTB 中 NMDA 表达降低(P<0.05)。左 MNTB 中较高的受体在 1 周时降低到我们未发现差异的水平(P>0.05),而 Gly-R 和 AMPA 甚至出现逆转(P<0.05)。(3)2 周时双侧 Gly 水平显著升高,左 MNTB 持续至 4 周(P<0.05)。
早期发育性 SSD 可导致 MNTB 中神经递质和受体的不对称分布,这可能是耳蜗植入后声音定位缺陷的根本原因。