Microglia Exit the CNS in Spinal Root Avulsion

Overview

Journal PLoS Biol

Specialty Biology

Date 2019 Feb 23

PMID 30794533

Citations 24

Authors

Lauren A Green

Julia C Nebiolo

Cody J Smith

Affiliations

Soon will be listed here.

Abstract

Microglia are central nervous system (CNS)-resident cells. Their ability to migrate outside of the CNS, however, is not understood. Using time-lapse imaging in an obstetrical brachial plexus injury (OBPI) model, we show that microglia squeeze through the spinal boundary and emigrate to peripheral spinal roots. Although both macrophages and microglia respond, microglia are the debris-clearing cell. Once outside the CNS, microglia re-enter the spinal cord in an altered state. These peripheral nervous system (PNS)-experienced microglia can travel to distal CNS areas from the injury site, including the brain, with debris. This emigration is balanced by two mechanisms-induced emigration via N-methyl-D-aspartate receptor (NMDA) dependence and restriction via contact-dependent cellular repulsion with macrophages. These discoveries open the possibility that microglia can migrate outside of their textbook-defined regions in disease states.

Citing Articles

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References

Kay J, Chu M, Sanes J . MEGF10 and MEGF11 mediate homotypic interactions required for mosaic spacing of retinal neurons. Nature. 2012; 483(7390):465-9. PMC: 3310952. DOI: 10.1038/nature10877. View

Zeidan-Chulia F, Salmina A, Malinovskaya N, Noda M, Verkhratsky A, Moreira J . The glial perspective of autism spectrum disorders. Neurosci Biobehav Rev. 2013; 38:160-72. DOI: 10.1016/j.neubiorev.2013.11.008. View

Peri F, Nusslein-Volhard C . Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo. Cell. 2008; 133(5):916-27. DOI: 10.1016/j.cell.2008.04.037. View

Greenhalgh A, Zarruk J, Healy L, Baskar Jesudasan S, Jhelum P, Salmon C . Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury. PLoS Biol. 2018; 16(10):e2005264. PMC: 6205650. DOI: 10.1371/journal.pbio.2005264. View

Binari L, Lewis G, Kucenas S . Perineurial glia require Notch signaling during motor nerve development but not regeneration. J Neurosci. 2013; 33(10):4241-52. PMC: 3668856. DOI: 10.1523/JNEUROSCI.4893-12.2013. View

Deczkowska A, Keren-Shaul H, Weiner A, Colonna M, Schwartz M, Amit I . Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration. Cell. 2018; 173(5):1073-1081. DOI: 10.1016/j.cell.2018.05.003. View

Zhuo M, Wu G, Wu L . Neuronal and microglial mechanisms of neuropathic pain. Mol Brain. 2011; 4:31. PMC: 3163530. DOI: 10.1186/1756-6606-4-31. View

Grueber W, Jan L, Jan Y . Tiling of the Drosophila epidermis by multidendritic sensory neurons. Development. 2002; 129(12):2867-78. DOI: 10.1242/dev.129.12.2867. View

Xu J, Zhu L, He S, Wu Y, Jin W, Yu T . Temporal-Spatial Resolution Fate Mapping Reveals Distinct Origins for Embryonic and Adult Microglia in Zebrafish. Dev Cell. 2015; 34(6):632-41. DOI: 10.1016/j.devcel.2015.08.018. View

10.

BARRON K . The microglial cell. A historical review. J Neurol Sci. 1995; 134 Suppl:57-68. DOI: 10.1016/0022-510x(95)00209-k. View

11.

Nichols E, Green L, Smith C . Ensheathing cells utilize dynamic tiling of neuronal somas in development and injury as early as neuronal differentiation. Neural Dev. 2018; 13(1):19. PMC: 6098834. DOI: 10.1186/s13064-018-0115-8. View

12.

Peng J, Gu N, Zhou L, Eyo U, Murugan M, Gan W . Microglia and monocytes synergistically promote the transition from acute to chronic pain after nerve injury. Nat Commun. 2016; 7:12029. PMC: 4931235. DOI: 10.1038/ncomms12029. View

13.

Neumann H, Kotter M, Franklin R . Debris clearance by microglia: an essential link between degeneration and regeneration. Brain. 2008; 132(Pt 2):288-95. PMC: 2640215. DOI: 10.1093/brain/awn109. View

14.

Schafer D, Lehrman E, Kautzman A, Koyama R, Mardinly A, Yamasaki R . Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012; 74(4):691-705. PMC: 3528177. DOI: 10.1016/j.neuron.2012.03.026. View

15.

Cunningham C, Martinez-Cerdeno V, Noctor S . Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J Neurosci. 2013; 33(10):4216-33. PMC: 3711552. DOI: 10.1523/JNEUROSCI.3441-12.2013. View

16.

Kreutzberg G . Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996; 19(8):312-8. DOI: 10.1016/0166-2236(96)10049-7. View

17.

Clark A, Gruber-Schoffnegger D, Drdla-Schutting R, Gerhold K, Malcangio M, Sandkuhler J . Selective activation of microglia facilitates synaptic strength. J Neurosci. 2015; 35(11):4552-70. PMC: 4363384. DOI: 10.1523/JNEUROSCI.2061-14.2015. View

18.

McGraw H, Nechiporuk A, Raible D . Zebrafish dorsal root ganglia neural precursor cells adopt a glial fate in the absence of neurogenin1. J Neurosci. 2008; 28(47):12558-69. PMC: 3176597. DOI: 10.1523/JNEUROSCI.2079-08.2008. View

19.

Kucenas S, Takada N, Park H, Woodruff E, Broadie K, Appel B . CNS-derived glia ensheath peripheral nerves and mediate motor root development. Nat Neurosci. 2008; 11(2):143-51. PMC: 2657597. DOI: 10.1038/nn2025. View

20.

Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch A, Cialic R . Differential roles of microglia and monocytes in the inflamed central nervous system. J Exp Med. 2014; 211(8):1533-49. PMC: 4113947. DOI: 10.1084/jem.20132477. View