Recent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair

Hart, Christopher G.; Karimi-Abdolrezaee, Soheila

doi:10.1002/jnr.24922

Cited by 51 publications

(24 citation statements)

References 442 publications

(681 reference statements)

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“…Previous research has shown that reactive astrogliosis, including astrocyte activation and migration, occurs upon injury [ 18 ]. To explore the influence of NOB on astrocyte migration induced by hypoxia, scratch wound healing assay was performed in this study.…”

Section: Resultsmentioning

confidence: 99%

“…Astrocytes are the major glial cells in the central nervous system (CNS), and play a critical role in the pathology of CNS. Due to their high sensitivity to changes in the microenvironment, astrocytes undergo a strong phenotypic transformation when damage occurs [ 18 ]. This process is called reactive astrogliosis, involving the activation and migration of astrocytes.…”

Section: Discussionmentioning

confidence: 99%

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Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Wang

Gao

et al. 2022

Molecules

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Increasing evidence indicates that nobiletin (NOB) is a promising neuroprotective agent. Astrocyte activation plays a key role in neurodegenerative disorders. Thus, this study aims to investigate the effects of NOB on astrocyte activation and the potential mechanisms. In this study, astrocytes were exposed to hypoxia injury for 24 h to induce activation in vitro. Glial fibrillary acidic protein (GFAP) was chosen as a marker of astrocyte activation. To evaluate the effects of NOB on the migration of activated astrocytes, we used a scratch wound healing assay and Transwell migration assay. In addition, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential, Nrf2 and HO-1 were measured to investigate the mechanisms of NOB in the activation of astrocytes. We found that NOB alleviated astrocyte activation and decreased GFAP expression during hypoxia. Simultaneously, NOB alleviated the migration of astrocytes induced by hypoxia. With NOB treatment, hypoxia-induced oxidative stress was partially reversed, including reducing the production of ROS and MDA. Furthermore, NOB significantly improved the mitochondrial dysfunction in activated astrocytes. Finally, NOB promoted Nrf2 nuclear translocation and HO-1 expression in response to continuous oxidative damage. Our study indicates, for the first time, that NOB alleviates the activation of astrocytes induced by hypoxia in vitro, in part by ameliorating oxidative stress and mitochondrial dysfunction. This provides new insights into the neuroprotective effects of NOB.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Wang

Gao

et al. 2022

Molecules

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“…The lesion core contains a mixture of activated fibroblasts, monocyte macrophages, and extracellular matrix proteins ( Figure 3 ) ( 106 ). Astrocytes are the most abundant glial cells in the CNS and play an important role in regulating blood flow, maintaining the integrity of the blood-brain barrier, modulating the plasticity and function of synapses, and keeping the balance of neuronal microenvironment ( 107 , 108 ). After SCI, astrocytes will proliferate, hypertrophy and gradually migrate along the edge of the severely damaged tissue, interweaving around the lesion center to form the main component of glial scar ( 109 – 111 ).…”

Section: Glial Scar Following Scimentioning

confidence: 99%

Neuroinflammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inflammation and Glial Scar

Pang

Chen

et al. 2021

Front. Immunol.

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Transected axons are unable to regenerate after spinal cord injury (SCI). Glial scar is thought to be responsible for this failure. Regulating the formation of glial scar post-SCI may contribute to axonal regrow. Over the past few decades, studies have found that the interaction between immune cells at the damaged site results in a robust and persistent inflammatory response. Current therapy strategies focus primarily on the inhibition of subacute and chronic neuroinflammation after the acute inflammatory response was executed. Growing evidences have documented that mesenchymal stem cells (MSCs) engraftment can be served as a promising cell therapy for SCI. Numerous studies have shown that MSCs transplantation can inhibit the excessive glial scar formation as well as inflammatory response, thereby facilitating the anatomical and functional recovery. Here, we will review the effects of inflammatory response and glial scar formation in spinal cord injury and repair. The role of MSCs in regulating neuroinflammation and glial scar formation after SCI will be reviewed as well.

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“…These cells provide energy metabolites to neurons (Pellerin et al, 1998 ; Fünfschilling et al, 2012 ; Lee et al, 2012 ), although energy insufficiency due to failed energy substrate provision is unlikely in this context because neuronal processes are suffused in a glucose-rich media in vitro . Nonetheless, oligodendrocytes and astrocytes confer axon support through multiple mechanisms that could be relevant in the context of ZIKV infection, such as regulating ion and glutamate homeostasis (Verkhratsky and Nedergaard, 2018 ; Hart and Karimi-Abdolrezaee, 2021 ), performing anti-oxidant functions (Baxter and Hardingham, 2016 ; Mukherjee et al, 2020 ), and enhancing axonal energy metabolism by deacetylating mitochondrial proteins (Chamberlain et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

SARM1 Depletion Slows Axon Degeneration in a CNS Model of Neurotropic Viral Infection

Crawford

Antoniou²,

Komarek

et al. 2022

Front. Mol. Neurosci.

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Zika virus (ZIKV) is a neurotropic flavivirus recently linked to congenital ZIKV syndrome in children and encephalitis and Guillain-Barré syndrome in adults. Neurotropic viruses often use axons to traffic to neuronal or glial cell somas where they either remain latent or replicate and proceed to infect new cells. Consequently, it has been suggested that axon degeneration could represent an evolutionarily conserved mechanism to limit viral spread. Whilst it is not known if ZIKV transits in axons, we previously reported that ZIKV infection of glial cells in a murine spinal cord-derived cell culture model of the CNS is associated with a profound loss of neuronal cell processes. This, despite that postmitotic neurons are relatively refractory to infection and death. Here, we tested the hypothesis that ZIKV-associated degeneration of neuronal processes is dependent on activation of Sterile alpha and armadillo motif-containing protein 1 (SARM1), an NADase that acts as a central executioner in a conserved axon degeneration pathway. To test this, we infected wild type and Sarm1 homozygous or heterozygous null cell cultures with ZIKV and examined NAD+ levels as well as the survival of neurons and their processes. Unexpectedly, ZIKV infection led to a rapid SARM1-independent reduction in NAD+. Nonetheless, the subsequent profound loss of neuronal cell processes was SARM1-dependent and was preceded by early changes in the appearance of β-tubulin III staining. Together, these data identify a role for SARM1 in the pathogenesis of ZIKV infection, which may reflect SARM1's conserved prodegenerative function, independent of its NADase activity.

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Recent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair

Cited by 51 publications

References 442 publications

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Neuroinflammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inflammation and Glial Scar

SARM1 Depletion Slows Axon Degeneration in a CNS Model of Neurotropic Viral Infection

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