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Docosahexaenoic acid reduces microglia phagocytic activity via miR-124 and induces neuroprotection in rodent models of spinal cord contusion injury
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2019
- Publisher :
- Oxford University Press, 2019.
-
Abstract
- Microglia are activated after spinal cord injury (SCI), but their phagocytic mechanisms and link to neuroprotection remain incompletely characterized. Docosahexaenoic acid (DHA) has been shown to have significant neuroprotective effects after hemisection and compression SCI and can directly affect microglia in these injury models. In rodent contusion SCI, we demonstrate that DHA (500 nmol/kg) administered acutely post-injury confers neuroprotection and enhances locomotor recovery, and also exerts a complex modulation of the microglial response to injury. In rodents, at 7 days after SCI, the level of phagocytosed myelin within Iba1-positive or P2Y12-positive cells was significantly lower after DHA treatment, and this occurred in parallel with an increase in intracellular miR-124 expression. Furthermore, intraspinal administration of a miR-124 inhibitor significantly reduced the DHA-induced decrease in myelin phagocytosis in mice at 7 days post-SCI. In rat spinal primary microglia cultures, DHA reduced the phagocytic response to myelin, which was associated with an increase in miR-124, but not miR-155. A similar response was observed in a microglia cell line (BV2) treated with DHA, and the effect was blocked by a miR-124 inhibitor. Furthermore, the phagocytic response of BV2 cells to stressed neurones was also reduced in the presence of DHA. In peripheral monocyte-derived macrophages, the expression of the M1, but not the M0 or M2 phenotype, was reduced by DHA, but the phagocytic activation was not altered. These findings show that DHA induces neuroprotection in contusion injury. Furthermore, the improved outcome is via a miR-124-dependent reduction in the phagocytic response of microglia.<br />US Department of Defence CDMRP/SCIRP award (W81XWH-10-1-1040 to P.K.Y., T.B. and A.M.T.); The Barts and London Charity (to P.K.Y. and A.M.T.); Rod Flower Vacation Scholarship (to A.L.B.); International Spinal Research Trust (to J.H. and P.G.P.); Ray W. Poppleton Endowment (to P.G.P.); Chang Gung Memorial Hospital, Taiwan (CMRPG3A1051–1054 to Z.-H.L.). M.A.B. is funded by the Spanish Ministry of Economy and Competitivity (Programa Ramón y Cajal: RYC-2017-21804).
- Subjects :
- medicine.medical_specialty
Spinal cord contusion
Phagocytosis
Contusions
Rodentia
Biology
Neuroprotection
PC12 Cells
Rats, Sprague-Dawley
03 medical and health sciences
Myelin
Mice
0302 clinical medicine
Internal medicine
Genetics
medicine
Spinal cord injuries
Animals
Molecular Biology
Spinal cord injury
Genetics (clinical)
Myelin Sheath
030304 developmental biology
Neurons
0303 health sciences
Microglia
Macrophages
Docosahexaenoic acids
General Medicine
medicine.disease
Rats
Mice, Inbred C57BL
Disease Models, Animal
MicroRNAs
medicine.anatomical_structure
Endocrinology
Neuroprotective Agents
Phenotype
Docosahexaenoic acid
Cell culture
Female
030217 neurology & neurosurgery
Intracellular
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....0733edd8ada34aa01120f917323e1fc4