MicroRNAs (miRNAs) are suspected to be a contributing factor in amyotrophic lateral sclerosis (ALS). Here, we assess the altered expression of miRNAs and the effects of miR-124 in astrocytic differentiation in neural stem cells of ALS transgenic mice. Differentially expressed miRNA-positive cells (including miR-124, miR-181a, miR-22, miR-26b, miR-34a, miR-146a, miR-219, miR-21, miR-200a, and miR-320) were detected by in situ hybridization and qRT-PCR in the spinal cord and the brainstem. Our results demonstrated that miR-124 was down-regulated in the spinal cord and brainstem. In vitro, miR-124 was down-regulated in neural stem cells and up-regulated in differentiated neural stem cells in G93A-superoxide dismutase 1 (SOD1) mice compared with WT mice by qRT-PCR. Meanwhile, Sox2 and Sox9 protein levels showed converse change with miR-124 in vivo and vitro. After over-expression or knockdown of miR-124 in motor neuron-like hybrid (NSC34) cells of mouse, Sox2 and Sox9 proteins were noticeably down-regulated or up-regulated, whereas Sox2 and Sox9 mRNAs remained virtually unchanged. Moreover, immunofluorescence results indicated that the number of double-positive cells of Sox2/glial fibrillary acidic protein (GFAP) and Sox9/glial fibrillary acidic protein (GFAP) was higher in G93A-SOD1 mice compared with WT mice. We also found that many Sox2- and Sox9-positive cells were nestin positive in G93A-SOD1 mice, but not in WT mice. Furthermore, differentiated neural stem cells from G93A-SOD1 mice generated a greater proportion of astrocytes and lower proportion of neurons than those from WT mice. MiR-124 may play an important role in astrocytic differentiation by targeting Sox2 and Sox9 in ALS transgenic mice. Cover Image for this issue: doi: 10.1111/jnc.14171.
Pubmed ID: 28960306 RIS Download
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This monoclonal targets Nestin (Rat-401) Mouse mAb
View all literature mentionsThis polyclonal targets Sox-9 (H-90)
View all literature mentionsThis monoclonal targets GFAP
View all literature mentionsThis monoclonal targets beta III Tubulin
View all literature mentionsThis polyclonal targets beta III Tubulin
View all literature mentionsCell line NSC-34 is a Hybrid cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsMus musculus with name B6SJL-Tg(SOD1*G93A)1Gur/J from IMSR.
View all literature mentionsThis monoclonal targets Nestin (Rat-401) Mouse mAb
View all literature mentionsThis monoclonal targets GFAP
View all literature mentionsThis polyclonal targets Sox-9 (H-90)
View all literature mentions