How lithium treatment generates neutrophilia by enhancing phosphorylation of GSK-3, increasing HIF-1 levels and how this path is important during engraftment

Kast, Richard E.

doi:10.1038/sj.bmt.1705872

Cited by 26 publications

(17 citation statements)

References 31 publications

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“…Published reports demonstrating GSK-3b modulation of HIF-1a and neurogenesis [26,27] prompted us to investigate this relationships in our model. Both HIF-1a and 2a expression levels in NSC and BEC were higher in CD1 cells compared to C57 cells (Fig.…”

Section: Potential Relationships Of Gsk-3b Hif-1a and 2a And Angio-amentioning

confidence: 92%

GSK-3β: a signaling pathway node modulating neural stem cell and endothelial cell interactions

Michaud

Canosa

et al. 2011

Angiogenesis

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The neurogenic areas of the brain are highly organized structures in which there is dynamic reciprocal modulation of neural stem cells (NSC) and microvascular endothelial cells (BEC) resulting in control of neural stem cell and vascular proliferation, survival and differentiation throughout the life of the individual. Select molecules such as GSK-3β, functioning as signaling nodes, and their downstream signaling components including HIF-1α, HIF-2α and β-catenin participate in regulating and orchestrating the diverse responses involved in this complex process. In this report we demonstrate GSK-3β's role as a signaling node in two mouse strains (C57BL/6, which have been found to respond to and recover from a hypoxic insult from P3 to P11 poorly and CD-1, which have been found to respond to and recover from a hypoxic insult from P3 to P11 well both in vivo and in vitro) which mimic the wide range of responsiveness to hypoxic insult observed in the very low birth weight premature infant population. Differences in levels of neural stem cell and microvascular endothelial cell GSK-3β activation, β-catenin serine phosphorylation, HIF-1α and 2α, BDNF, SDF-1 and VEGF, β-III-tubulin and cleaved notch-1 expression in C57BL/6 and CD-1 subventricular zone tissues, and cultured NSC and BEC were noted. Specifically, CD1 pups, SVZ tissues and isolated NSC and BEC exhibit less GSK-3β and β-catenin serine phoslphorylation and greater HIF-1α and 2α, BDNF, SDF-1 and VEGF, β-III-tubulin and cleaved notch-1 expression compared to C57BL/6. Correlating with these changes were differences of several neural stem cell and microvascular endothelial cell behaviors including proliferation, apoptosis, migration and differentiation with CD1 NSC exhibiting greater proliferation and migration and decreased apoptosis and differentiation and CD1 BEC exhibiting greater angiogenesis. Further, upon treatment with nanomolar concentrations of a GSK-3β inhibitor (SB412682), C57 NSC and BEC behaviors could be brought to CD1 levels, consistent with the concept of GSK-3β functioning as a multifunctional signaling pathway node, modulating several behaviors in these cells. Lastly, the therapeutic potential of targeting GSK-3β is discussed.

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Section: Potential Relationships Of Gsk-3b Hif-1a and 2a And Angio-amentioning

confidence: 92%

GSK-3β: a signaling pathway node modulating neural stem cell and endothelial cell interactions

Michaud

Canosa

et al. 2011

Angiogenesis

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“…Both agents induce neutrophilia via differing mechanisms. Lithium has been demonstrated to potentiate the action of CXCL12, which has a direct trophic effect on neutrophil production (Kast, 2008). G-CSF is a cytokine that directly stimulates proliferation and terminal granulocytic differentiation of haematopoietic precursors through a variety of molecular pathways (Kaushansky, 2006).…”

Section: Introductionmentioning

confidence: 99%

Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations

Myles

Clark

Bird

et al. 2017

Aust N Z J Psychiatry

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Background: Clozapine is the most effective medication for treatment-refractory schizophrenia; however, its use is contraindicated in people who have had previous clozapine-induced neutropenia. Co-prescription of granulocyte-colony stimulating factor may prevent recurrent neutropenia and allow continuation or rechallenge of clozapine.Objective and methods: Systematic review of literature reporting the use of granulocyte-colony stimulating factor to allow rechallenge or continuation of clozapine in people with previous episodes of clozapine-induced neutropenia. The efficacy of granulocyte-colony stimulating factor and predictors of successful rechallenge will be determined to elucidate whether evidence-based recommendations can be made regarding the use of granulocyte-colony stimulating factor in this context. Results:A total of 17 articles were identified that reported on clozapine rechallenge with granulocyte-colony stimulating factor support. In all, 76% of cases were able to continue clozapine at median follow-up of 12 months. There were no clear clinical or laboratory predictors of successful rechallenge; however, initial neutropenia was more severe in successful cases compared to unsuccessful cases. Cases co-prescribed lithium had lower success rates of rechallenge (60%) compared to those who were not prescribed lithium (81%). The most commonly reported rechallenge strategy was use of filgrastim 150-480 µg between daily to three times a week. There were no medication-specific side effects of granulocyte-colony stimulating factor reported apart from euphoria in one case. Three cases who failed granulocytecolony stimulating factor had bacterial infection at time of recurrent neutropenia. No deaths were reported. Conclusion:Preliminary data suggest granulocyte-colony stimulating factor is safe and effective in facilitating rechallenge with clozapine. Clinical recommendations for use are discussed.

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“…However, lithium-mediated pro-inflammatory effects have been described as well (18). Most interestingly, lithium-mediated inhibition of GSK-3 was recently shown to result in increased neutrophil production and release of lysosomal enzymes (19). This effect has been linked with several cutaneous side effects of lithium therapy [reviewed in (20)] and might well account for the development of UD lesions, a prominent hallmark of which is a massive neutrophil infiltration.…”

Section: Discussionmentioning

confidence: 99%

Experimental analysis of risk factors for ulcerative dermatitis in mice

Neuhaus

Niessen

Mesaros

et al. 2012

Experimental Dermatology

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Ulcerative dermatitis (UD) is a severe inflammatory skin disorder with an unknown aetiology. Recently, insulin receptor substrate 1 KO mice were shown to be fully resistant to UD. In this study, we showed that high-fat diet (HFD) feeding significantly increased incidence of UD in wild type (WT) C57BL/6 mice, as did lithium-mediated inhibition of GSK3-b, which is a key negative regulator of IRS1. In contrast to WT mice, resistance to UD was fully preserved in HFD-fed Irs1-KO mice. Our results identify IRS1 as a key determinant of UD pathogenesis and establish a direct link between diet composition, obesity-induced inflammation and chronic ulceration.

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How lithium treatment generates neutrophilia by enhancing phosphorylation of GSK-3, increasing HIF-1 levels and how this path is important during engraftment

Cited by 26 publications

References 31 publications

GSK-3β: a signaling pathway node modulating neural stem cell and endothelial cell interactions

GSK-3β: a signaling pathway node modulating neural stem cell and endothelial cell interactions

Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations

Experimental analysis of risk factors for ulcerative dermatitis in mice

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