Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2

Spinelli, Marialuigia; Boucard, Céline; Ornaghi, Sara; Schoeberlein, Andreina; Keller, Irene; Coman, Daniel; Hyder, Fahmeed; Zhang, Longbo; Haesler, Valérie; Bordey, Angélique; Barnea, Eytan R.; Paidas, Michael J.; Surbek, Daniel; Mueller, Martin

doi:10.1172/jci.insight.132335

Cited by 6 publications

(12 citation statements)

References 61 publications

(124 reference statements)

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“…Therefore, we decided to detect mGRPs progeny in the brains next 26 . Notably, glial precursors differentiate into astrocytes and oligodendrocytes and sPIF may affect their differentiation capacity 17 , 29 , 30 . Transplantation of mGRPs- GFP+ cells in the ALS transgenic mouse model (SOD1 G93A ) resulted in few GFP + astrocytes and oligodendrocytes in the brain parenchyma and this was evident in the sPIF group only (Figs.…”

Section: Resultsmentioning

confidence: 99%

“…5 , 6 , 7 and 8 ), the role of sPIF (alone or synergistic with mGRPs) is currently unclear. However, the neuroprotective effects of sPIF in both neonatal and adult murine models of brain injury open the possibility that sPIF alone may be neuroprotective in the ALS model as well 12 , 13 , 16 , 17 . The second successful immune modulatory drug was CB.…”

Section: Discussionmentioning

confidence: 99%

“…The question whether sPIF alone would have been sufficient or if the mGRPs/sPIF would produce a synergistic effect needs further investigation. Given that sPIF is neuroprotective, crosses the blood–brain barrier, and already received a FAST-Track FDA approval (autoimmune diseases of non-pregnant subjects clinicaltrials.gov, NCT02239562), the clinical use could be very promising 12 , 13 , 17 , 28 , 36 , 37 .…”

Section: Discussionmentioning

confidence: 99%

“…The immune modulatory regimes were chosen based on previous reports of successful immune modulation and neuroprotective property 11 , 17 , 39 – 41 .…”

Section: Methodsmentioning

confidence: 99%

“…sPIF was able to reverse and prevent paralysis and restore myelination through inhibiting neuro-inflammation in murine models of experimental autoimmune encephalomyelitis 16 . The neuroprotective property of sPIF was further underscored by its ability to mitigate neuronal loss and microglial activation in murine model of immature brain injury as well 9 , 12 , 13 , 17 . Tac is a calcineurin inhibitor and a first-line immunosuppressive drug used after organ transplant 18 , which additionally may enhance neuronal regeneration 19 .…”

Section: Introductionmentioning

confidence: 99%

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Murine glial progenitor cells transplantation and synthetic PreImplantation Factor (sPIF) reduces inflammation and early motor impairment in ALS mice

Ambrożkiewicz

Kozlowska

Haesler

et al. 2022

Sci Rep

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Amyotrophic lateral sclerosis (ALS) is a progressive motor neuronal disorder characterized by neuronal degeneration and currently no effective cure is available to stop or delay the disease from progression. Transplantation of murine glial-restricted precursors (mGRPs) is an attractive strategy to modulate ALS development and advancements such as the use of immune modulators could potentially extend graft survival and function. Using a well-established ALS transgenic mouse model (SOD1G93A), we tested mGRPs in combination with the immune modulators synthetic PreImplantation Factor (sPIF), Tacrolimus (Tac), and Costimulatory Blockade (CB). We report that transplantation of mGRPs into the cisterna magna did not result in increased mice survival. The addition of immunomodulatory regimes again did not increase mice lifespan but improved motor functions and sPIF was superior compared to other immune modulators. Immune modulators did not affect mGRPs engraftment significantly but reduced pro-inflammatory cytokine production. Finally, sPIF and CB reduced the number of microglial cells and prevented neuronal number loss. Given the safety profile and a neuroprotective potential of sPIF, we envision its clinical application in near future.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The immune modulatory regimes were chosen based on previous reports of successful immune modulation and neuroprotective property 11 , 17 , 39 – 41 .…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Murine glial progenitor cells transplantation and synthetic PreImplantation Factor (sPIF) reduces inflammation and early motor impairment in ALS mice

Ambrożkiewicz

Kozlowska

Haesler

et al. 2022

Sci Rep

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Effect of electroacupuncture on global cerebral ischemia‑reperfusion injury in rats: A urine proteome analysis

Zhang,

Dai,

et al. 2024

Brain and Behavior

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BackgroundThis study aimed to investigate dynamic urinary proteome changes of electroacupuncture (EP) on cerebral ischemia‑reperfusion (CI/R) injured rats and to explore the therapeutic biological mechanisms of EP.MethodsFirst, changed urinary proteins were found in EP stimulation in healthy rats. Then, we used a CI/R injury rat model induced by Pulsinelli's four‐vessel occlusion (4‐VO) method to explore the function of EP on urinary proteome in CI/R injury. Urine samples were collected for proteome analysis by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) and bioinformatics analysis.ResultsIn total, 384 proteins were identified, among which 47 proteins (23 upregulated, 24 downregulated) were differentially expressed with 0.6‐log FC and p < .05. Gene ontology analysis revealed that the cell redox homeostasis, acute‐phase response, response to lipopolysaccharide, and cellular response to glucocorticoid stimulus were significantly enriched. The partially biologically connected differential proteins were found by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis in the EP group. With the CI/R rat model, 80 proteins (27 upregulated, 53 downregulated) were significantly changed in the CI/R rats compared to the controls. Among these differentially expressed proteins (DEPs), 23 proteins (17 upregulated, six downregulated) showed significant changes after EP treatment (0.6‐log FC change, p < .05). The main related biological processes were aging, immune response, acute‐phase response, liver regeneration, protein catabolic process, and response to oxidative stress. Many metabolic pathways were enriched by KEGG analysis.ConclusionOur results indicate that the EP could alleviate cerebral damage induced by ischemia‑reperfusion through an anti‐inflammatory and metabolism regulation mechanism. The urinary proteome might reflect the pathophysiological changes in EP pretreatment in the treatment and prevention of CI/R injury.

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LncRNA H19 knockdown promotes neuropathologic and functional recovery via the Nrf2/HO‐1 axis after traumatic brain injury

Chen,

Wu,

Shi

et al. 2024

CNS Neurosci Ther

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AimsTraumatic brain injury (TBI) stands as a significant concern in public health, frequently leading to enduring neurological deficits. Long non‐coding RNA H19 (lncRNA H19) exerts a potential regulator role in the pathology of brain injury. This study investigates the effects of lncRNA H19 knockdown (H19‐KD) on the pathophysiology of TBI and its potential neuroprotective mechanisms.MethodsControlled cortical impact was employed to establish a stable TBI mouse model. The expression levels of various genes in perilesional cortex and striatum tissue after TBI was detected by RT‐qPCR. AAV9‐shRNA‐H19 was injected into the lateral ventricle of mice to knockdown the expression of lncRNA H19. Various behavioral tests were performed to evaluate sensorimotor and cognitive functions after TBI. Immunofluorescence and Nissl staining were performed to assess brain tissue damage and neuroinflammation. The Nrf2 and HO‐1 expression was performed by Western blot.ResultsAfter TBI, the expression of lncRNA H19 was elevated in perilesional tissue and gradually reverted to baseline. Behavioral tests demonstrated that H19‐KD significantly promoted the recovery of sensorimotor and cognitive functions after TBI. Besides, H19‐KD reduced brain tissue loss, preserved neuronal integrity, and ameliorated white matter damage at the histological level. In addition, H19‐KD restrained the pro‐inflammatory and facilitated anti‐inflammatory phenotypes of microglia/macrophages, attenuating the neuroinflammatory response after TBI. Furthermore, H19‐KD promoted activation of the Nrf2/HO‐1 axis after TBI, while suppression of Nrf2 partially abolished the neuroprotective effect.ConclusionH19‐KD exerts neuroprotective effects after TBI in mice, partially mediated by the activation of the Nrf2/HO‐1 axis.

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Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2

Cited by 6 publications

References 61 publications

Murine glial progenitor cells transplantation and synthetic PreImplantation Factor (sPIF) reduces inflammation and early motor impairment in ALS mice

Murine glial progenitor cells transplantation and synthetic PreImplantation Factor (sPIF) reduces inflammation and early motor impairment in ALS mice

Effect of electroacupuncture on global cerebral ischemia‑reperfusion injury in rats: A urine proteome analysis

LncRNA H19 knockdown promotes neuropathologic and functional recovery via the Nrf2/HO‐1 axis after traumatic brain injury

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