Microglia-derived exosomes modulate myelin regeneration via activating Nrf2 signaling pathway in oligodendrocyte
Jia-Yi He1, Xiao-Yu Ji1, Bo Huang2
1National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China.
Abstract:
Demyelination is a prominent feature of multiple sclerosis (MS), where the ability of damaged areas to regenerate myelin is limited. Oligodendrocyte precursor cells (OPCs) accumulate in these areas but struggle to mature into oligodendrocytes (OLGs). Microglia also gather at the lesion site, but their impact on OPCs differentiation is not well understood. Here, we found that miR-155-5p was significantly elevated in the expression profile of exosomes extracted from activated microglia. This miRNA binds to the 3' UTR of the transcription factor Nrf2 in OPCs, inhibiting their differentiation. In a mouse model of demyelination induced by cuprizone, inhibiting miR-155-5p in microglia led to improved motor function recovery, increased the number of mature oligodendrocytes and promoted remyelination. In this study, we highlight a potential new target for treating demyelinating diseases.
Insights
Microglia-derived miR-155-5p inhibits oligodendrocyte precursor cell (OPC) differentiation in demyelination. Inhibiting this microRNA in microglia promotes remyelination and motor recovery in a mouse model, offering a potential therapeutic target for multiple sclerosis.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Multiple sclerosis (MS) is characterized by limited myelin regeneration in damaged areas.
- Oligodendrocyte precursor cells (OPCs) accumulate but fail to mature into oligodendrocytes (OLGs) in MS lesions.
- The role of microglia in OPC differentiation during demyelination remains unclear.
Purpose of the Study:
- To investigate the role of microglial exosomes in OPC differentiation.
- To identify specific microRNAs involved in the inhibition of OPC maturation.
- To explore therapeutic strategies targeting microglial communication in demyelinating diseases.
Main Methods:
- Exosomes were extracted from activated microglia.
- MicroRNA expression profiling was performed.
- Inhibition of miR-155-5p in a cuprizone-induced mouse model of demyelination.
- Assessment of motor function, oligodendrocyte maturation, and remyelination.
Main Results:
- miR-155-5p expression was significantly elevated in microglial exosomes.
- miR-155-5p directly targets Nrf2 in OPCs, inhibiting their differentiation.
- Inhibition of miR-155-5p in microglia improved motor function, increased mature oligodendrocytes, and promoted remyelination in mice.
Conclusions:
- Microglial miR-155-5p plays a critical role in suppressing OPC differentiation.
- Targeting miR-155-5p in microglia represents a promising therapeutic avenue for demyelinating diseases like MS.
- This study elucidates a novel mechanism of microglial-oligodendroglial interaction in myelin repair.
Related Concept Videos
01:15Neurogenesis and Regeneration of Nervous Tissue
01:25Nervous Tissue: Myelin
Schwann cells begin to form myelin sheaths around axons during fetal development. They wrap around a small...