Genomics

Dataset Information

39

MiRNA profile in lumbar spinal cord homogenate from healthy controls and ALS


ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a paralytic degenerative disease of the nervous system. In the SOD1 mouse model of ALS we found loss of the molecular and functional microglia signature associated with pronounced expression of miR-155 in SOD1 mice. We also found increased expression of miR-155 in the spinal cord of ALS subjects. Genetic ablation of miR-155 increased survival in SOD1 mice and reversed the abnormal microglial and monocyte molecular signature. In addition, dysregulated proteins in the spinal cord of SOD1 mice that we identified in human ALS spinal cords and CSF were restored in SOD1G93A/miR155-/- mice. Treatment of SOD1 mice with anti-miR-155 SOD1 mice injected systemically or into the cerebrospinal fluid prolonged survival and restored the microglial unique genetic and microRNA profiles. Our findings provide a new avenue for immune based therapy of ALS by targeting miR-155. Overall design: Total RNA was isolated from whole spinal cord homogenate - post mortem obtained from healthy donors without known neurologic diseases and from sALS and fALS donors. Total RNA was extracted using mirVanaTM miRNA isolation kit (Ambion) according to the manufacturer’s protocol. nCounter Nansotring human miRNA assay kit was used for miRNA expression profile

INSTRUMENT(S): Nanostring Human miRNA Assay Kit (mirBase 17)

SUBMITTER: Oleg Butovsky  

PROVIDER: GSE52670 | GEO | 2014-11-24

SECONDARY ACCESSION(S): PRJNA230490

REPOSITORIES: GEO

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Publications


To investigate miR-155 in the SOD1 mouse model and human sporadic and familial amyotrophic lateral sclerosis (ALS).NanoString microRNA, microglia and immune gene profiles, protein mass spectrometry, and RNA-seq analyses were measured in spinal cord microglia, splenic monocytes, and spinal cord tissue from SOD1 mice and in spinal cord tissue of familial and sporadic ALS. miR-155 was targeted by genetic ablation or by peripheral or centrally administered anti-miR-155 inhibitor in SOD1 mice.In SOD1  ...[more]

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