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囊泡谷氨酸转运体3在发育中的转圈小鼠的耳蜗内毛细胞和螺旋神经节细胞中强烈上调。

Vesicular glutamate transporter 3 is strongly upregulated in cochlear inner hair cells and spiral ganglion cells of developing circling mice.

作者信息

Lee Youngeun, Kim Hak Rim, Ahn Seung Cheol

机构信息

Department of Nanobio Medical Science, Dankook University, 119 Dandaero, Anseo-dong, Cheonan-si, Chungnam 330-714, Republic of Korea.

Department of Pharmacology, College of Medicine, Dankook University, 119 Dandaero, Anseo-dong, Cheonan-si, Chungnam 330-714, 119 Dandaero, Republic of Korea.

出版信息

Neurosci Lett. 2015 Jan 1;584:320-4. doi: 10.1016/j.neulet.2014.10.053. Epub 2014 Nov 3.

DOI:10.1016/j.neulet.2014.10.053
PMID:25450145
Abstract

Vesicular glutamate transporter 3 (VGLUT3) plays a major role in hearing, and mice lacking the VGLUT3 are congenitally deaf due to absence of glutamate release at the inner hair cell afferent synapses. However, whether VGLUT3 is expressed normally in the cochleae of developing circling mice (homozygous (cir/cir) mice), the animal model for human deafness type DFNB6, has not been established. In this study, we investigated the developmental expression of VGLUT3 in cochlear inner hair cells (IHCs) and spiral ganglion cells (SGCs) of homozygous (cir/cir) mice from postnatal day (P)1 to P14 using immunofluorescence (IF) staining and Western blot. VGLUT3 immunoreactivity (IR) and protein expression increased progressively with age in homozygous (cir/cir) and control mice (heterozygous (+/cir) mice and ICR mice). The rank order of VGLUT3 IR in IHCs and SGCs in P14 mice was homozygous (cir/cir) mice = heterozygous (+/cir) mice > ICR mice. The rank order of total protein expression was homozygous (cir/cir) mice > heterozygous (+/cir) mice = ICR mice at P14. IF staining and Western blot analysis indicated that developmental VGLUT3 expression in cochleae was most prominent in homozygous (cir/cir) mice. The possible contribution of VGLUT3 upregulation in the cochlear degeneration is discussed.

摘要

囊泡型谷氨酸转运体3(VGLUT3)在听力中起主要作用,缺乏VGLUT3的小鼠由于内毛细胞传入突触处谷氨酸释放缺失而先天性耳聋。然而,VGLUT3在人类耳聋DFNB6型动物模型——发育中的回旋小鼠(纯合子(cir/cir)小鼠)的耳蜗中是否正常表达尚未确定。在本研究中,我们使用免疫荧光(IF)染色和蛋白质印迹法,研究了纯合子(cir/cir)小鼠从出生后第(P)1天到P14天耳蜗内毛细胞(IHC)和螺旋神经节细胞(SGC)中VGLUT3的发育表达。在纯合子(cir/cir)小鼠和对照小鼠(杂合子(+/cir)小鼠和ICR小鼠)中,VGLUT3免疫反应性(IR)和蛋白质表达随年龄逐渐增加。P14小鼠的IHC和SGC中VGLUT3 IR的排序为纯合子(cir/cir)小鼠 = 杂合子(+/cir)小鼠 > ICR小鼠。在P14时,总蛋白质表达的排序为纯合子(cir/cir)小鼠 > 杂合子(+/cir)小鼠 = ICR小鼠。IF染色和蛋白质印迹分析表明,耳蜗中VGLUT3的发育表达在纯合子(cir/cir)小鼠中最为突出。本文讨论了VGLUT3上调在耳蜗变性中的可能作用。

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