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Int J Clin Exp Pathol 2013;6(9):1826-1838

Original Article
miRNA-9 expression is upregulated in the spinal cord of G93A-SOD1 transgenic mice

Fenghua Zhou, Yingjun Guan, Yanchun Chen, Caixia Zhang, Li Yu, Hailing Gao, Hongmei Du, Bing Liu, Xin Wang

Department of Pathology, Weifang Medical University, Weifang, Shandong, P. R. China; Department of Histology and Embryology, Weifang
Medical University, Weifang, Shandong, P. R. China; Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School,
Boston, MA, USA

Received June 29, 2013; Accepted August 3, 2013; Epub August 15, 2013; Published September 1, 2013

Abstract: The pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. Accumulating evidence indicates that various miRNAs
expressed in a spatially and temporally controlled manner in the nervous system have an important function in the development of
neurodegenerative diseases. The present study aimed to determine the expression and cellular distribution of miRNA-9 in the spinal cord of
G93A-SOD1 mutant mice at different time points (post-natal 95, 108 and 122 d). miRNA expression was evaluated by microarray analysis;
differentially expressed miRNAs were validated by RT-qPCR. The cellular distribution of miRNA-9 was analyzed by in-situ hybridization.
Microarray results indicated for the first time that various miRNAs were differentially expressed between the G93A-SOD1 mutant mice and the
littermate control mice. miRNA-9 expression was upregulated at 95, 108, and 122 d as validated by microarray analysis, RT-qPCR, and ISH.
ISH results also showed that the miRNA-9-positive cells mainly expressed in the cytoplasm were located in the dorsal horn and the ventral
horn of the spinal cord. The majority of miRNA-9-positive cells were located in the ventral horn of the gray matter, the locus of
neurodegeneration. These results indicated that the differential expression of miRNA-9 may have an important function in the pathogenesis of
G93A-SOD1 transgenic mice.

Keywords: ALS, miRNA-9, differential expression

Address correspondence to: Dr. Yingjun Guan, Department of Histology and Embryology, Weifang Medical University, Shandong 261053,
China. Fax: 86-0536-8271216; E-mail: guanyj@wfmc.edu.cn; Dr. Xin Wang, Department of Neurosurgery, BLI141 and LMRC 111, Brigham and
Women’s Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA. Fax: +1 617-278-6937; E-mail: xwang@rics.bwh.harvard.edu