Local proliferation is the main source of rod microglia after optic nerve transection

Yuan, Ti Fei; Yu, Liang; Peng, Bo; Lin, Bin; So, Kwok-Fai

doi:10.1038/srep10788

Cited by 45 publications

(59 citation statements)

References 25 publications

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“…We showed that bipolar/rod-shaped microglia aligned only within the scratched area of the PDL/laminin-coated surface, and the alignment patterns were similar to those observed in the brain after CNS injury in vivo 91016. The microglia became amoeboid on the non-scratched area of the PDL/laminin-coated surface5.…”

supporting

confidence: 69%

The association between laminin and microglial morphology in vitro

Tam

Eddie

2016

Sci Rep

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Microglia are immune cells in the central nervous system (CNS) that contribute to primary innate immune responses. The morphology of microglia is closely associated with their functional activities. The majority of microglial studies have focused on the ramified or amoeboid morphology; however, bipolar/rod-shaped microglia have recently received much attention. Bipolar/rod-shaped microglia form trains with end-to-end alignment in injured brains and retinae, which is proposed as an important mechanism in CNS repair. We previously established a cell culture model system to enrich bipolar/rod-shaped microglia simply by growing primary microglia on scratched poly-D-lysine (PDL)/laminin-coated surfaces. Here, we investigated the role of laminin in morphological changes of microglia. Bipolar/rod-shaped microglia trains were transiently formed on scratched surfaces without PDL/laminin coating, but the microglia alignment disappeared after 3 days in culture. Amoeboid microglia digested the surrounding laminin, and the gene and protein expression of laminin-cleaving genes Adam9 and Ctss was up-regulated. Interestingly, lipopolysaccharide (LPS)-induced transformation from bipolar/rod-shaped into amoeboid microglia increased the expression of Adam9 and Ctss, and the expression of these genes in LPS-treated amoeboid-enriched cultures remained unchanged. These results indicate a strong association between laminin and morphological transformation of microglia, shedding new light on the role of bipolar/rod-shaped microglia in CNS repair.

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supporting

confidence: 69%

The association between laminin and microglial morphology in vitro

Tam

Eddie

2016

Sci Rep

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“…In another mouse model of amyotrophic lateral sclerosis that represented chronic, long-lasting damage, these same results were achieved [13]. Consistent with these findings, local proliferation of resident microglia, rather than the infiltration of peripheral monocytes or HSCs, was the major source of Brod^microgliosis in an optical nerve transection model using parabiosis rats [33]. Taken together, the maintenance of the CNS microglia pool only relies on the resident cells without irradiation and BM transplantation and is irrelevant to the timing of microgliosis.…”

Section: Maintenance Of Microglia Poolsupporting

confidence: 85%

Friend or Foe? Resident Microglia vs Bone Marrow-Derived Microglia and Their Roles in the Retinal Degeneration

et al. 2016

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Microglia are immune cells in the central nervous system (CNS) that originate from the yolk sac in an embryo. The renewal of the microglia pool in the adult eye consists of two components. In addition to the self-proliferation of resident cells, microglia in the CNS also derive from the bone marrow (BM). BM-derived cells pass through the blood-brain barrier (BBB) or blood-retina barrier (BRB) and differentiate into microglia under specific conditions which involves a complex mechanism. Recent studies have widely investigated the role of resident microglia and BM-derived microglia in the retinal degenerative disease. Both two cell types play dual roles and share many similar functions. However, resident microglia tend to polarize to the M1 phenotype which is pro-inflammatory and neurotoxic, whereas BM-derived microglia mainly polarize to the neuroprotective M2 phenotype in retinal degeneration. The molecular mechanism that underlines the invasion of peripheral cells has led to extensive discussions. In addition to the BBB and BRB disruption, many signaling pathways are involved in this process. Based on these studies, we discuss the roles of these two types of microglia in retinal degeneration disease and the potential clinical application of BM-derived microglia, which may benefit future therapies.

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“…It is also important to highlight that rod microglia formed with limited proliferation. This is in contrast to other contexts, such as retinal rod microglia following optic nerve crush, where rod microglia result from proliferation (Yuan et al, ). Collectively, these data show that rod microglia develop from resident microglia that were present at the time of injury and underwent structural transformation in response to neuronal injury.…”

Section: Discussionmentioning

confidence: 79%

“…Rod‐shaped microglia form as early as 1 dpi, peak in the subacute window, and align linearly in the cortex 7 dpi (Taylor, Morganti‐Kossmann, Lifshitz, & Ziebell, ). This structure is observed in other pathological contexts, including aging and chronic viral infection (Bachstetter et al, ; Ji, Schachtschneider, Schook, Walker, & Johnson, ; Sierra et al, ; Yuan, Liang, Peng, Lin, & So, ). Thus, it may represent a conserved response to neuronal degeneration/damage.…”

Section: Introductionmentioning

confidence: 81%

Traumatic brain injury‐induced neuronal damage in the somatosensory cortex causes formation of rod‐shaped microglia that promote astrogliosis and persistent neuroinflammation

Witcher

Bray

Dziabis

et al. 2018

Glia

124

119

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Microglia undergo dynamic structural and transcriptional changes during the immune response to traumatic brain injury (TBI). For example, TBI causes microglia to form rod‐shaped trains in the cerebral cortex, but their contribution to inflammation and pathophysiology is unclear. The purpose of this study was to determine the origin and alignment of rod microglia and to determine the role of microglia in propagating persistent cortical inflammation. Here, diffuse TBI in mice was modeled by midline fluid percussion injury (FPI). Bone marrow chimerism and BrdU pulse‐chase experiments revealed that rod microglia derived from resident microglia with limited proliferation. Novel data also show that TBI‐induced rod microglia were proximal to axotomized neurons, spatially overlapped with dense astrogliosis, and aligned with apical pyramidal dendrites. Furthermore, rod microglia formed adjacent to hypertrophied microglia, which clustered among layer V pyramidal neurons. To better understand the contribution of microglia to cortical inflammation and injury, microglia were eliminated prior to TBI by CSF1R antagonism (PLX5622). Microglial elimination did not affect cortical neuron axotomy induced by TBI, but attenuated rod microglial formation and astrogliosis. Analysis of 262 immune genes revealed that TBI caused profound cortical inflammation acutely (8 hr) that progressed in nature and complexity by 7 dpi. For instance, gene expression related to complement, phagocytosis, toll‐like receptor signaling, and interferon response were increased 7 dpi. Critically, these acute and chronic inflammatory responses were prevented by microglial elimination. Taken together, TBI‐induced neuronal injury causes microglia to structurally associate with neurons, augment astrogliosis, and propagate diverse and persistent inflammatory/immune signaling pathways.

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Local proliferation is the main source of rod microglia after optic nerve transection

Cited by 45 publications

References 25 publications

The association between laminin and microglial morphology in vitro

The association between laminin and microglial morphology in vitro

Friend or Foe? Resident Microglia vs Bone Marrow-Derived Microglia and Their Roles in the Retinal Degeneration

Traumatic brain injury‐induced neuronal damage in the somatosensory cortex causes formation of rod‐shaped microglia that promote astrogliosis and persistent neuroinflammation

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