T0901317, a liver X receptor agonist, ameliorates perinatal white matter injury induced by ischemia and hypoxia in neonatal rats

Gao, Ting; Qian, Tianyang; Wang, Tianwei; Su, Yu; Qiu, Han; Tang, Wan; Xing, Qinghe; Wang, Laishuan

doi:10.1016/j.neulet.2022.136994

Cited by 5 publications

(5 citation statements)

References 50 publications

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“…LXRs are activated by oxysterol catabolites in the presence of oxygen, and their expression is reduced during hypoxia and hypoperfusion. 62 , 63 However, upon reperfusion oxysterol production is supposedly restored (as we observe by the upregulation of Ch25h in microglia) and the following activation of LXRs results in increased expression of ABC transporters (e.g., Abca1 and Abcg1 ). Macrophages can modulate the inflammatory response by activating LXRs that are able to trans -repress nuclear factor κB (NF-κB) signaling.…”

Section: Discussionmentioning

confidence: 65%

Inflammatory, metabolic, and sex-dependent gene-regulatory dynamics of microglia and macrophages in neonatal hippocampus after hypoxia-ischemia

Di Martino,

Ambikan,

Ramsköld

et al. 2024

iScience

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Section: Discussionmentioning

confidence: 65%

Inflammatory, metabolic, and sex-dependent gene-regulatory dynamics of microglia and macrophages in neonatal hippocampus after hypoxia-ischemia

Di Martino,

Ambikan,

Ramsköld

et al. 2024

iScience

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“…We demonstrate that agents targeting the effect of Nef on ABCA1 prevent Nef-induced oligodendrocyte damage in vitro. The LXR agonist TO-901317, known for its potent induction of ABCA1, has previously been shown to enhance oligodendrocyte proliferation, differentiation, and maturation, and to alleviate ischemia and lysolecithin-induced demyelination [ 83 , 84 ]. Although TO-901317 treatment resulted in an overall increase in O4 + cells, we observed two distinct oligodendrocyte morphologies in cultures treated with TO-901317: more mature oligodendrocytes with highly complex branching and less mature oligodendrocytes with fewer branching processes.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles produced by HIV-1 Nef-expressing cells induce myelin impairment and oligodendrocyte damage in the mouse central nervous system

Schenck,

Karl,

Clarkson-Paredes

et al. 2024

J Neuroinflammation

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HIV-associated neurocognitive disorders (HAND) are a spectrum of cognitive impairments that continue to affect approximately half of all HIV-positive individuals despite effective viral suppression through antiretroviral therapy (ART). White matter pathologies have persisted in the ART era, and the degree of white matter damage correlates with the degree of neurocognitive impairment in patients with HAND. The HIV protein Nef has been implicated in HAND pathogenesis, but its effect on white matter damage has not been well characterized. Here, utilizing in vivo, ex vivo, and in vitro methods, we demonstrate that Nef-containing extracellular vesicles (Nef EVs) disrupt myelin sheaths and inflict damage upon oligodendrocytes within the murine central nervous system. Intracranial injection of Nef EVs leads to reduced myelin basic protein (MBP) staining and a decreased number of CC1 + oligodendrocytes in the corpus callosum. Moreover, cerebellar slice cultures treated with Nef EVs exhibit diminished MBP expression and increased presence of unmyelinated axons. Primary mixed brain cultures and enriched oligodendrocyte precursor cell cultures exposed to Nef EVs display a decreased number of O4 + cells, indicative of oligodendrocyte impairment. These findings underscore the potential contribution of Nef EV-mediated damage to oligodendrocytes and myelin maintenance in the pathogenesis of HAND.

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“…The OLN‐93 cell line, identified as immature oligodendrocyte from rat brain, was utilized to explore signaling pathway of OLs in vitro 33,34 . OLN‐93 cells were donated by Department of Neonatology, Children's Hospital of Fudan University, China.…”

Section: Methodsmentioning

confidence: 99%

“…The OLN-93 cell line, identified as immature oligodendrocyte from rat brain, was utilized to explore signaling pathway of OLs in vitro. 33,34 OLN-93 cells were donated by Department of Neonatology, Children's Hospital of Fudan University, China. These cells were cultured with medium (Dulbecco's modified Eagle's medium, 10% fetal bovine serum plus), and were divided into six groups as follows: Sham group, oxygen glucose deprivation (OGD) group, OGD + PTN group, OGD+ PBS group, OGD + PTN + Everolimus group, and OGD + PTN + DMSO group.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Pleiotrophin ameliorates white matter injury of neonatal rats by activating the mTOR/YY1/Id4 signaling pathway

Qiu

Zhou

et al. 2023

The FASEB Journal

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Brain white matter injury (WMI) is a serious disease of the central nervous system. Pleiotrophin (PTN) promotes the differentiation and myelination of oligodendrocytes (OLs) in vitro. However, the role of PTN in WMI remains unknown. Therefore, this study aimed to investigate the neuroprotective role and potential mechanisms of PTN function in neonatal rats with WMI. The PTN and mammalian target of rapamycin (mTOR) inhibitor everolimus was used to treat a WMI model in postnatal day 3 Sprague–Dawley rats, in which the right common carotid arteries of these rats were isolated, ligated, and exposed to a hypoxic environment (6% O2 + 94% N2) for 2 h. OL differentiation and myelination, as well as the spatial learning and memory abilities of the rats were evaluated to examine the effects of PTN. Two proteins of the mTOR signaling pathway, YingYang1 (YY1) and inhibitor of DNA binding 4 (Id4), were detected and were used to explore the potential mechanisms of PTN in rat WMI experiment and oxygen glucose deprivation (OGD) model. We found that the differentiation and myelination of OLs were impaired after WMI. PTN administration rescued this injury by activating mTOR/YY1 and inhibiting Id4. Everolimus administration inhibited mTOR/YY1 and activated Id4, which blocked the neuroprotective role of PTN in WMI. PTN plays a neuroprotective role in neonatal rats with WMI, which could be involved in the mTOR/YY1/Id4 signaling pathway.

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T0901317, a liver X receptor agonist, ameliorates perinatal white matter injury induced by ischemia and hypoxia in neonatal rats

Cited by 5 publications

References 50 publications

Inflammatory, metabolic, and sex-dependent gene-regulatory dynamics of microglia and macrophages in neonatal hippocampus after hypoxia-ischemia

Inflammatory, metabolic, and sex-dependent gene-regulatory dynamics of microglia and macrophages in neonatal hippocampus after hypoxia-ischemia

Extracellular vesicles produced by HIV-1 Nef-expressing cells induce myelin impairment and oligodendrocyte damage in the mouse central nervous system

Pleiotrophin ameliorates white matter injury of neonatal rats by activating the mTOR/YY1/Id4 signaling pathway

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