Early morphofunctional plasticity of microglia in response to acute lipopolysaccharide

Madore, Charlotte; Joffre, Corinne; Delpech, Jean-Christophe; Smedt-Peyrusse, Véronique de; Aubert, Agnès; Coste, L.; Layé, Sophie; Nadjar, Agnès

doi:10.1016/j.bbi.2013.08.008

Cited by 56 publications

(42 citation statements)

References 42 publications

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“…In addition, most or all of the cells expressed macrophage markers CD14, HLA-DR, CD16, CD206, CD163, Iba1 and iNOS. All the morphological types that we observed in cultures during manufacturing are similar to the variety of morphologies that have been described in preparations of human macrophage, including brain macrophage and microglia [10–12]. DUOC-01 may also be related to donor microglial cells present in the brains of patients months after transplantation [3].…”

Section: Discussionsupporting

confidence: 67%

Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases

et al. 2015

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Background aims Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period. Methods DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by direct biochemical analysis; alloreactivity of DUOC-01 and of peripheral blood (PB) mononuclear cells (MNC) to DUOC-01 by mixed lymphocyte culture methods; and cytokine secretion by Bioplex assays. Results DUOC-01 cultures contained highly active, attached, motile, slowly proliferating cells that expressed common (cluster of differentiation [CD]11b, CD14 and Iba1), M1 type (CD16, inducible nitric oxide synthase), and M2-type (CD163, CD206) macrophage or microglia markers. Activities of 11 disease-relevant lysosomal enzymes in DUOC-01 products were similar to those of normal PB cells. All DUOC-01 products secreted interleukin (IL)-6 and IL-10. Accumulation of transforming growth factor-β, IL-1β, interferon-γ and TNF-α in supernatants was variable. IL-12, IL-2, IL-4, IL-5 and IL-13 were not detected at significant concentrations. Galactocerebrosidase, transforming growth factor-β and IL-10 transcripts were specifically enriched in DUOC-01 relative to CB cells. PB MNCs proliferated and released cytokines in response to DUOC-01. DUOC-01 did not proliferate in response to mismatched MNC. Conclusions DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases.

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Section: Discussionsupporting

confidence: 67%

Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases

et al. 2015

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“…In a model of retina lesion, CX 3 CR1 has been shown to be implicated in the fast response of microglia toward the lesion (Liang et al, 2009). Interestingly, in vivo activated microglia by bacterial endotoxin such as lipopolysaccharide (LPS) exhibit retracted ramifications (Madore et al, 2013), this in response to ATP detected by the adenosine receptor 2A (Orr et al, 2009). Activation of this receptor could explain morphological changes from ramified to amoeboid microglia.…”

Section: Microglia Role In Neuronal Surveillancementioning

confidence: 97%

Microglia in neuronal plasticity: Influence of stress

et al. 2015

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“…Fluorescence was determined on an ABI PRISM 7500-sequence detection system (Applied Biosystems, California, USA). Data were analyzed using the comparative threshold cycle (Ct) method, results are expressed as relative fold change (Mingam et al, 2008;Madore et al, 2013;Madore et al, 2014;Delpech et al, 2015a) to control target mRNA expression.…”

Section: Treatmentsmentioning

confidence: 99%

“…RNA purity and concentration were determined using a Nanodrop spectrophotometer (Nanodrop technologies, Wilmington, DE). One µg of RNA was reverse transcribed to synthesize cDNA using Superscript III (Invitrogen, Life Technologies TM ) and random hexamers according to the manufacturer's protocol (Labrousse et al, 2012;Madore et al, 2013;Madore et al, 2014;Delpech et al, 2015a). Quantitative PCR was performed to measure cytokine expression using the Applied Biosystems (California, USA) assay-on demand gene expression protocol as previously described (Mingam et al, 2008;Delpech et al, 2015a).…”

Section: Treatmentsmentioning

confidence: 99%

Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment

Delpech

Thomazeau

Madore

et al. 2015

Neuropsychopharmacol

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Dietary n-3 polyunsaturated fatty acids (PUFAs) are critical components of inflammatory response and memory impairment. However, the mechanisms underlying the sensitizing effects of low n-3 PUFAs in the brain for the development of memory impairment following inflammation are still poorly understood. In this study, we examined how a 2-month n-3 PUFAs deficiency from pre-puberty to adulthood could increase vulnerability to the effect of inflammatory event on spatial memory in mice. Mice were given diets balanced or deficient in n-3 PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS), a bacterial endotoxin, at adulthood. We first showed that spatial memory performance was altered after LPS challenge only in n-3 PUFA-deficient mice that displayed lower n-3/n-6 PUFA ratio in the hippocampus. Importantly, long-term depression (LTD), but not long-term potentiation (LTP) was impaired in the hippocampus of LPS-treated n-3 PUFA-deficient mice. Proinflammatory cytokine levels were increased in the plasma of both n-3 PUFA-deficient and n-3 PUFA-balanced mice. However, only n-3 PUFA-balanced mice showed an increase in cytokine expression in the hippocampus in response to LPS. In addition, n-3 PUFA-deficient mice displayed higher glucocorticoid levels in response to LPS as compared with n-3 PUFA-balanced mice. These results indicate a role for n-3 PUFA imbalance in the sensitization of the hippocampal synaptic plasticity to inflammatory stimuli, which is likely to contribute to spatial memory impairment.

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Early morphofunctional plasticity of microglia in response to acute lipopolysaccharide

Cited by 56 publications

References 42 publications

Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases

Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases

Microglia in neuronal plasticity: Influence of stress

Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment

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