VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination

Miyamoto, Yuki; Torii, Tomohiro; Tanoue, Akito; Yamauchi, Junji

doi:10.1038/ncomms13478

Cited by 41 publications

(34 citation statements)

References 50 publications

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“…Several transcription factors are involved in the maturation of OPCs, such as Olig2, Nkx2.2, which promotes the maturation of OPCs [28,29]. Rcent research has suggested that VCAM1 knockout mice exhibit reduced myelin thickness, VCAM1 contributes to the initiation of myelination [30]. The present results showed that the ratio of NG2/Olig2positive OPCs remarkably decreased in the corpus callosum at 14 days after ischemia-hypoxia.…”

Section: Discussionsupporting

confidence: 52%

Clemastine Improves Hypomyelination in Rats with Hypoxic–Ischemic Brain Injury by Reducing Astroglia-Derived IL-1β via Autophagy

Xie¹,

Niu²,

Gao³

et al. 2020

Preprint

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Background Cardiac arrest can lead to a poor prognosis of the nervous system. Neuroinflammation plays an important role in hypoxic ischemic brain injury (HIBI). Regulation of inflammation via autophagy might be a suitable therapeutic target in HIBI. This study aims to determine whether clemastine can improve hypomyelination by suppressing the activated astrocytes via autophagy and improving axonal hypomyelination in HIBI.Methods A bilateral common carotid artery occlusion (BCCAO) rat model that received continuous intraperitoneal injection (1 mg/kg) for 14 days was employed to elaborate the neuroprotection effects of clemastine. interleukin-1β (IL-1β), nod-like receptor protein 3 (NLRP3), histamine H1 receptor, autophagy related protein and OPCs differentiation levels in the corpus callosum were measured. Primary cultured OPCs and co-culture of astrocytes and OPCs were used to explore the link between astrocytes activation and hypomyelination. Data were evaluated by one-way ANOVA with Fisher’s protected least significant difference test.Results Clemastine treatment could reverse hypomyelination and restrain the upregulation of IL-1β and NLRP3 in the corpus callosum of BCCAO rats. Primary cultured OPCs treated with IL-1β showed failed maturation. Expression of LC3Ⅱ/Ⅰdecreased after astrocytic activation. Co-culture of astrocytes and OPCs with oxygen glucose deprivation treatment exhibited NLRP3/1β upregulation and PLP downregulation. Clemastine could downregulate NLRP3/1β and reverse hypomyelination by promoting the autophagy.Conclusions Clemastine could improve axonal hypomyelination by inhibiting astrocytes activation via promoting the autophagy in BCCAO rats, thus might be a viable strategy to inhibit hypomyelination in the corpus callosum of patients with HIBI.

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Section: Discussionsupporting

confidence: 52%

Clemastine Improves Hypomyelination in Rats with Hypoxic–Ischemic Brain Injury by Reducing Astroglia-Derived IL-1β via Autophagy

Xie¹,

Niu²,

Gao³

et al. 2020

Preprint

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“…Microglia mediate inflammatory responses in the CNS, but are also known to directly affect neurons, and vice versa, in the developing human as well as rodent CNS 4 , 6 , 28 , 29 . Recently, it has been established that microglia can initiate synaptogenesis, but also eliminate synapses during development and in disease 5 , 8 , 29 . Here, we began to probe the applicability of cerebral organoids for studying the interplay between human microglia and neurons, and for studying microglia-mediated inflammatory responses in situ.…”

Section: Resultsmentioning

confidence: 99%

Microglia innately develop within cerebral organoids

et al. 2018

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Cerebral organoids are 3D stem cell-derived models that can be utilized to study the human brain. The current consensus is that cerebral organoids consist of cells derived from the neuroectodermal lineage. This limits their value and applicability, as mesodermal-derived microglia are important players in neural development and disease. Remarkably, here we show that microglia can innately develop within a cerebral organoid model and display their characteristic ramified morphology. The transcriptome and response to inflammatory stimulation of these organoid-grown microglia closely mimic the transcriptome and response of adult microglia acutely isolated from post mortem human brain tissue. In addition, organoid-grown microglia mediate phagocytosis and synaptic material is detected inside them. In all, our study characterizes a microglia-containing organoid model that represents a valuable tool for studying the interplay between microglia, macroglia, and neurons in human brain development and disease.

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“…9f). Genes such as cathepsin L (Ctsl), semaphorin 5A (Sema5a), and synaptotagminlike 2 (Sytl2) are highly expressed by differentiating OLs 49 , whereas vascular cell-adhesion molecule (Vcam1), sodiumcalcium exchanger-solute carrier family 8 member A3 (Slc8a3), and disheveled-associated activator of morphogenesis 2 (Daam2) play a causal role in OL differentiation or myelination [50][51][52] .…”

Section: Resultsmentioning

confidence: 99%

Environmental enrichment ameliorates perinatal brain injury and promotes functional white matter recovery

et al. 2020

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Hypoxic damage to the developing brain due to preterm birth causes many anatomical changes, including damage to the periventricular white matter. This results in the loss of glial cells, significant disruptions in myelination, and thereby cognitive and behavioral disabilities seen throughout life. Encouragingly, these neurological morbidities can be improved by environmental factors; however, the underlying cellular mechanisms remain unknown. We found that early and continuous environmental enrichment selectively enhances endogenous repair of the developing white matter by promoting oligodendroglial maturation, myelination, and functional recovery after perinatal brain injury. These effects require increased exposure to socialization, physical activity, and cognitive enhancement of surroundings-a complete enriched environment. Using RNA-sequencing, we identified oligodendroglial-specific responses to hypoxic brain injury, and uncovered molecular mechanisms involved in enrichment-induced recovery. Together, these results indicate that myelin plasticity induced by modulation of the neonatal environment can be targeted as a therapeutic strategy for preterm birth.

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VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination

Cited by 41 publications

References 50 publications

Clemastine Improves Hypomyelination in Rats with Hypoxic–Ischemic Brain Injury by Reducing Astroglia-Derived IL-1β via Autophagy

Clemastine Improves Hypomyelination in Rats with Hypoxic–Ischemic Brain Injury by Reducing Astroglia-Derived IL-1β via Autophagy

Microglia innately develop within cerebral organoids

Environmental enrichment ameliorates perinatal brain injury and promotes functional white matter recovery

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