M2 microglia promotes neurogenesis and oligodendrogenesis from neural stem/progenitor cells via the PPARγ signaling pathway

Yuan, Jianmin; Ge, Hongfei; Liu, Wei; Zhu, Haitao; Chen, Yaxing; Zhou, Xuan; Yang, Yang; Yin, Yi; Chen, Weixiang; Wu, Weiqiang; Yang, Yifeng; Lin, Jiangkai

doi:10.18632/oncotarget.15774

Cited by 73 publications

(58 citation statements)

References 35 publications

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“…For example, MRC2, Axl, SPP1, Clec7a, Pdcd1, Lgals3, and Fabp5 are known to push macrophages into M2 phenotype (Burke, Kerr, Moriarty, Finn, & Roche, ; Jiao, Natoli, Valter, Provis, & Rutar, ; Moore, Holt, Malpass, Hines, & Wheeler, ; Petruzzi, Cherubini, Salum, & de Figueiredo, ; Rahimian, Beland, & Kriz, ; Yao et al, ; Zhang, Du, Chen, & Xiang, ). The M2 anti‐inflammatory mode is known to be protective for neurogenesis (Yuan et al, ). Some inflammatory M1‐related genes were also found (Csf2ra, Cxcl10).…”

Section: Resultsmentioning

confidence: 99%

Unique role for dentate gyrus microglia in neuroblast survival and in VEGF‐induced activation

Kreisel

Wolf

Keshet

et al. 2018

Glia

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Neurogenic roles of microglia (MG) are thought to include an active role in adult hippocampal neurogenesis in addition to their established roles in pruning surplus dendrites and clearing dead neuroblasts. However, identification of such a role and its delineation in the neurogenic cascade is yet to be established. Using diphtheria toxin‐aided MG ablation, we show that MG reduction in the DG—the site where neuronal stem cells (NSCs) reside—is sufficient to impede overall hippocampal neurogenesis due to reduced survival of newly formed neuroblasts. To examine whether MG residing in the hippocampal neurogenic zone are inherently different from MG residing elsewhere in the hippocampus, we compared growth factor responsiveness of DG MG with that of CA1 MG. Strikingly, transgenic induction of the potent neurogenic factor VEGF elicited robust on‐site MG expansion and activation exclusively in the DG and despite eliciting a comparable angiogenic response in the CA1 and elsewhere. Temporally, DG‐specific MG expansion preceded both angiogenic and neurogenic responses. Remarkably, even partial MG reduction during the process of VEGF‐induced neurogenesis led to reducing the number of newly formed neuroblasts to the basal level. Transcriptomic analysis of MG retrieved from the naïve DG and CA1 uncovered a set of genes preferentially expressed in DG MG. Notably the tyrosine kinase Axl is exclusively expressed in naïve and VEGF‐induced DG MG and its inhibition prevented neurogenesis augmentation by VEGF. Taken together, findings uncover inherent unique properties of DG MG of supporting both basal‐ and VEGF‐induced adult hippocampal neurogenesis.

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Section: Resultsmentioning

confidence: 99%

Unique role for dentate gyrus microglia in neuroblast survival and in VEGF‐induced activation

Kreisel

Wolf

Keshet

et al. 2018

Glia

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“…Anti-inflammatory microglia have been reported to peak 3 days after a stroke and play an essential role in synapse remodeling through the release of microgliaderived BDNF [6,17]. They additionally play an essential role in synapse transmission through the remyelination of axons after a stroke via the modulation of oligodendrogenesis [11,34]. However, chronically active microglia have been shown to be responsible for the late demyelination occurring after stroke [35].…”

Section: Discussionmentioning

confidence: 99%

Microglia knockdown reduces inflammation and preserves cognition in diabetic animals after experimental stroke

Jackson

Dumanli

Johnson

et al. 2020

J Neuroinflammation

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Introduction: Unfortunately, over 40% of stroke victims have pre-existing diabetes which not only increases their risk of stroke up to 2-6 fold, but also worsens both functional recovery and the severity of cognitive impairment. Our lab has recently linked the chronic inflammation in diabetes to poor functional outcomes and exacerbated cognitive impairment, also known as post-stroke cognitive impairment (PSCI). Although we have shown that the development of PSCI in diabetes is associated with the upregulation and the activation of pro-inflammatory microglia, we have not established direct causation between the two. To this end, we evaluated the role of microglia in the development of PSCI.Methods: At 13 weeks of age, diabetic animals received bilateral intracerebroventricular (ICV) injections of short hairpin RNA (shRNA) lentiviral particles targeting the colony stimulating factor 1 receptor (CSF1R). After 14 days, animals were subjected to 60 min middle cerebral artery occlusion (MCAO) or sham surgery. Adhesive removal task (ART), novel object recognition (NOR), and 2-trial Y-maze were utilized to evaluate sensorimotor and cognitive function. Tissue from freshly harvested brains was analyzed by flow cytometry and immunohistochemistry.Results: CSF1R silencing resulted in a 94% knockdown of residential microglia to relieve inflammation and improve myelination of white matter in the brain. This prevented cognitive decline in diabetic animals. Conclusion: Microglial activation after stroke in diabetes may be causally related to the development of delayed neurodegeneration and PSCI.

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“…Specific assessment of M1 (classical) and M2 (alternative) polarization upon exposure to DE would be useful to elucidate this issue. The mode of microglial activation may promote or inhibit NPC proliferation, cause them to embark upon a glial rather than a neuronal lineage, or favor either survival or apoptosis (Yuan et al 2017). Another possibility is the phagocytosis of stressed but viable developing neurons by microglia, in a process called “phagoptosis” (Brown and Neher 2014).…”

Section: Discussionmentioning

confidence: 99%

Acute exposure to diesel exhaust impairs adult neurogenesis in mice: prominence in males and protective effect of pioglitazone

et al. 2018

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Adult neurogenesis is the process by which neural stem cells give rise to new functional neurons in specific regions of the adult brain, a process that occurs throughout life. Significantly, neurodegenerative and psychiatric disorders present suppressed neurogenesis, activated microglia, and neuroinflammation. Traffic-related air pollution has been shown to adversely affect the central nervous system. As the cardinal effects of air pollution exposure are microglial activation, and ensuing oxidative stress and neuroinflammation, we investigated whether acute exposures to diesel exhaust (DE) would inhibit adult neurogenesis in mice. Mice were exposed for 6 h to DE at a PM concentration of 250-300 μg/m, followed by assessment of adult neurogenesis in the hippocampal subgranular zone (SGZ), the subventricular zone (SVZ), and olfactory bulb (OB). DE impaired cellular proliferation in the SGZ and SVZ in males, but not females. DE reduced adult neurogenesis, with male mice showing fewer new neurons in the SGZ, SVZ, and OB, and females showing fewer new neurons only in the OB. To assess whether blocking microglial activation protected against DE-induced suppression of adult hippocampal neurogenesis, male mice were pre-treated with pioglitazone (PGZ) prior to DE exposure. The effects of DE exposure on microglia, as well as neuroinflammation and oxidative stress, were reduced by PGZ. PGZ also antagonized DE-induced suppression of neurogenesis in the SGZ. These results suggest that DE exposure impairs adult neurogenesis in a sex-dependent manner, by a mechanism likely to involve microglia activation and neuroinflammation.

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M2 microglia promotes neurogenesis and oligodendrogenesis from neural stem/progenitor cells via the PPARγ signaling pathway

Cited by 73 publications

References 35 publications

Unique role for dentate gyrus microglia in neuroblast survival and in VEGF‐induced activation

Unique role for dentate gyrus microglia in neuroblast survival and in VEGF‐induced activation

Microglia knockdown reduces inflammation and preserves cognition in diabetic animals after experimental stroke

Acute exposure to diesel exhaust impairs adult neurogenesis in mice: prominence in males and protective effect of pioglitazone

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