Overexpression of miR-124 in Motor Neurons Plays a Key Role in ALS Pathological Processes
| Autor: | Ana Rita Colaço, Ana Rita Vaz, Daniela Vizinha, Marta Barbosa, Dora Brites, Hermes Morais, Gecioni Loch-Neckel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
amyotrophic lateral sclerosis motor neuron regeneration Mice Superoxide Dismutase-1 paracrine signaling regulation Biology (General) Spectroscopy Motor Neurons spinal microglia Microglia motor neuron secretome Neurogenesis Neurodegeneration General Medicine Mitochondria Computer Science Applications Cell biology Chemistry medicine.anatomical_structure miR-124 modulation Female Synaptic signaling Signal Transduction mSOD1 mice model Neurite QH301-705.5 Mice Transgenic inflamma-miRNAs Biology Catalysis Article neuro-immune deregulation Inorganic Chemistry Downregulation and upregulation microRNA medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology QD1-999 Organic Chemistry medicine.disease Mice Inbred C57BL Disease Models Animal MicroRNAs Axoplasmic transport spinal organotypic cultures Biomarkers |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 6128, p 6128 (2021) International Journal of Molecular Sciences Volume 22 Issue 11 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | miRNA(miR)-124 is an important regulator of neurogenesis, but its upregulation in SOD1G93A motor neurons (mSOD1 MNs) was shown to associate with neurodegeneration and microglia activation. We used pre-miR-124 in wild-type (WT) MNs and anti-miR-124 in mSOD1 MNs to characterize the miR-124 pathological role. miR-124 overexpression in WT MNs produced a miRNA profile like that of mSOD1 MNs (high miR-125b low miR-146a and miR-21), and similarly led to early apoptosis. Alterations in mSOD1 MNs were abrogated with anti-miR-124 and changes in their miRNAs mostly recapitulated by their secretome. Normalization of miR-124 levels in mSOD1 MNs prevented the dysregulation of neurite network, mitochondria dynamics, axonal transport, and synaptic signaling. Same alterations were observed in WT MNs after pre-miR-124 transfection. Secretome from mSOD1 MNs triggered spinal microglia activation, which was unno-ticed with that from anti-miR-124-modulated cells. Secretome from such modulated MNs, when added to SC organotypic cultures from mSOD1 mice in the early symptomatic stage, also coun-teracted the pathology associated to GFAP decrease, PSD-95 and CX3CL1-CX3CR1 signaling im-pairment, neuro-immune homeostatic imbalance, and enhanced miR-124 expression levels. Data suggest that miR-124 is implicated in MN degeneration and paracrine-mediated pathogenicity. We propose miR-124 as a new therapeutic target and a promising ALS biomarker in patient sub-populations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|