Recent Advances in the Study of Bipolar/Rod-Shaped Microglia and their Roles in Neurodegeneration

Au, Ngan Pan Bennett; Eddie, Chi Him

doi:10.3389/fnagi.2017.00128

Cited by 54 publications

(57 citation statements)

References 167 publications

(286 reference statements)

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“…In humans, changes in microglial shape serve as indicators of specific pathological processes in the CNS. The appearance of bipolar rod microglia is a hallmark of activation in many CNS diseases 58 . In glaucoma, bipolar rod microglia are associated with neurodegeneration and ocular hypertension 59 .…”

Section: Discussionmentioning

confidence: 99%

Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics

et al. 2020

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Tissue microarchitecture and mechanics are important in development and pathologies of the Central Nervous System (CNS); however, their coordinating mechanisms are unclear. Here, we report that during colonization of the retina, microglia contacts the deep layer of high stiffness, which coincides with microglial bipolarization, reduction in TGFβ1 signaling and termination of vascular growth. Likewise, stiff substrates induce microglial bipolarization and diminish TGFβ1 expression in hydrogels. Both microglial bipolarization in vivo and the responses to stiff substrates in vitro require intracellular adaptor Kindlin3 but not microglial integrins. Lack of Kindlin3 causes high microglial contractility, dysregulation of ERK signaling, excessive TGFβ1 expression and abnormally-patterned vasculature with severe malformations in the area of photoreceptors. Both excessive TGFβ1 signaling and vascular defects caused by Kindlin3-deficient microglia are rescued by either microglial depletion or microglial knockout of TGFβ1 in vivo. This mechanism underlies an interplay between microglia, vascular patterning and tissue mechanics within the CNS.

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Section: Discussionmentioning

confidence: 99%

Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics

et al. 2020

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“…This type of interaction has also been reported in other human neurological and psychiatric disorders that include viral infections and dementia ( 11 , 46 ). Evidence suggests that the interactions between rod microglia and dendrites also occur following brain injury ( 14 , 47 ). While the physiological significance of rod-shaped microglia and their tight interactions with dendritic processes remains to be defined, it has been argued that rod microglia may be required to prevent further damage to injured areas ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

“…Evidence suggests that the interactions between rod microglia and dendrites also occur following brain injury ( 14 , 47 ). While the physiological significance of rod-shaped microglia and their tight interactions with dendritic processes remains to be defined, it has been argued that rod microglia may be required to prevent further damage to injured areas ( 47 ). In addition, it is also possible that the microglia–dendritic contacts, independent of microglial morphology, may result in synaptic stripping ( 48 – 50 ).…”

Section: Discussionmentioning

confidence: 99%

Status Epilepticus Triggers Time-Dependent Alterations in Microglia Abundance and Morphological Phenotypes in the Hippocampus

2017

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Status epilepticus (SE) is defined by the occurrence of prolonged “non-stop” seizures that last for at least 5 min. SE provokes inflammatory responses including the activation of microglial cells, the brain’s resident immune cells, which are thought to contribute to the neuropathology and pathophysiology of epilepsy. Microglia are professional phagocytes that resemble peripheral macrophages. Upon sensing immune disturbances, including SE, microglia become reactive, produce inflammatory cytokines, and alter their actin cytoskeleton to transform from ramified to amoeboid shapes. It is widely known that SE triggers time-dependent microglial expression of pro-inflammatory cytokines that include TNFα and IL-1β. However, less is known in regards to the spatiotemporal progression of the morphological changes, which may help define the extent of microglia reactivity after SE and potential function (surveillance, inflammatory, phagocytic). Therefore, in this study, we used the microglia/macrophage IBA1 marker to identify and count these cells in hippocampi from control rats and at 4 h, 3 days, and 2 weeks after a single episode of pilocarpine-induced SE. We identified, categorized, and counted the IBA1-positive cells with the different morphologies observed after SE in the hippocampal areas CA1, CA3, and dentate gyrus. These included ramified, hypertrophic, bushy, amoeboid, and rod. We found that the ramified phenotype was the most abundant in control hippocampi. In contrast, SE provoked time-dependent changes in the microglial morphology that was characterized by significant increases in the abundance of bushy-shaped cells at 4 h and amoeboid-shaped cells at 3 days and 2 weeks. Interestingly, a significant increase in the number of rod-shaped cells was only evident in the CA1 region at 2 weeks after SE. Taken together, these data suggest that SE triggers time-dependent alterations in the morphology of microglial cells. This detailed description of the spatiotemporal profile of SE-induced microglial morphological changes may help provide insight into their contribution to epileptogenesis.

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“…Recently, it has been shown the potential neuro-protective role of bipolar/rod-shaped microglia. Indeed, the spatial arrangement of bipolar/rod-shaped microglia seems to play a role in the reorganization and remodeling of neuronal circuitry following CNS injuries [52]. Our findings, showing the transition towards bipolar/ rod-shaped microglia after a-MWCNT cell exposure, rather than a switch towards the amoeboid shape, as observed after MWCNTs exposure, and the induction of the release of anti-inflammatory cytokines and neurotrophic factors after 48 h exposure, seem extremely important to support the capacity of electro-conductive a-MWCNTs to modulate brain cells behavior and functions towards neuroprotective effects.…”

Section: Discussionmentioning

confidence: 99%

Switching on microglia with electro-conductive multi walled carbon nanotubes

Fiorito

Russier

Salemme

et al. 2018

Carbon

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OATAO is an open access repository that collects the work of Toulouse researchers and makes it freely available over the web where possible. This is an author-deposited version published in : http://oatao. a b s t r a c tWe explored the mechanisms underlying microglia cell-carbon nanotube interactions in order to investigate whether electrical properties of Carbon-Nanotubes (CNTs) could affect microglia brain cells function and phenotype. We analyzed the effects induced by highly electro-conductive Multi-WalledCarbon-Nanotubes (a-MWCNTs), on microglia cells from rat brain cortex and compared the results with those obtained with as prepared not conductive MWCNTs (MWCNTs) and redox-active Double-WalledCarbon-Nanotubes (DWCNTs). Cell viability and CNT capacity to stimulate the release of nitric oxide (NO), pro-inflammatory (IL-1b, TNF-a) and anti-inflammatory (IL-10, TGF-b1) cytokines and neurotrophic factors (mNGF) were assessed.Electro-conductive MWCNTs, besides not being cytotoxic, were shown to stimulate, at 24 h cell exposure, classical "M1 00 microglia activation phenotype, increasing significantly the release of the main pro-inflammatory cytokines. Conversely, after 48 h cell exposure, they induced the transition from classical "M1 00 to alternative "M2 00 microglia phenotype, supported by anti-inflammatory cytokines and neuroprotective factor mNGF release. The analysis of cell morphology change, by tubulin and CD-206 þ labelling showed that M2 phenotype was much more expressed at 48 h in cells exposed to aMWCNTs than in untreated cells.Our data suggest that the intrinsic electrical properties of CNTs could be exploited to modulate microglia phenotype and function stimulating microglia anti-inflammatory potential.

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Recent Advances in the Study of Bipolar/Rod-Shaped Microglia and their Roles in Neurodegeneration

Cited by 54 publications

References 167 publications

Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics

Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics

Status Epilepticus Triggers Time-Dependent Alterations in Microglia Abundance and Morphological Phenotypes in the Hippocampus

Switching on microglia with electro-conductive multi walled carbon nanotubes

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