Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Dusica Maysinger
  • Dominic Gröger
  • Andrew Lake
  • Kai Licha
  • Marie Weinhart
  • Philip K.Y. Chang
  • Rose Mulvey
  • Rainer Haag
  • R. Anne McKinney

Externe Organisationen

  • McGill University
  • Freie Universität Berlin (FU Berlin)
  • mivenion GmbH
  • Imperial College London
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Details

OriginalspracheEnglisch
Seiten (von - bis)3073-3082
Seitenumfang10
FachzeitschriftBiomacromolecules
Jahrgang16
Ausgabenummer9
Frühes Online-Datum12 Aug. 2015
PublikationsstatusVeröffentlicht - 14 Sept. 2015
Extern publiziertJa

Abstract

Hyperactivity of microglia and loss of functional circuitry is a common feature of many neurological disorders including those induced or exacerbated by inflammation. Herein, we investigate the response of microglia and changes in hippocampal dendritic postsynaptic spines by dendritic polyglycerol sulfate (dPGS) treatment. Mouse microglia and organotypic hippocampal slices were exposed to dPGS and an inflammogen (lipopolysaccharides). Measurements of intracellular fluorescence and confocal microscopic analyses revealed that dPGS is avidly internalized by microglia but not CA1 pyramidal neurons. Concentration and time-dependent response studies consistently showed no obvious toxicity of dPGS. The adverse effects induced by proinflammogen LPS exposure were reduced and dendritic spine morphology was normalized with the addition of dPGS. This was accompanied by a significant reduction in nitrite and proinflammatory cytokines (TNF-α and IL-6) from hyperactive microglia suggesting normalized circuitry function with dPGS treatment. Collectively, these results suggest that dPGS acts anti-inflammatory, inhibits inflammation-induced degenerative changes in microglia phenotype and rescues dendritic spine morphology.

ASJC Scopus Sachgebiete

Zitieren

Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits. / Maysinger, Dusica; Gröger, Dominic; Lake, Andrew et al.
in: Biomacromolecules, Jahrgang 16, Nr. 9, 14.09.2015, S. 3073-3082.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Maysinger, D, Gröger, D, Lake, A, Licha, K, Weinhart, M, Chang, PKY, Mulvey, R, Haag, R & McKinney, RA 2015, 'Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits', Biomacromolecules, Jg. 16, Nr. 9, S. 3073-3082. https://doi.org/10.1021/acs.biomac.5b00999
Maysinger, D., Gröger, D., Lake, A., Licha, K., Weinhart, M., Chang, P. K. Y., Mulvey, R., Haag, R., & McKinney, R. A. (2015). Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits. Biomacromolecules, 16(9), 3073-3082. https://doi.org/10.1021/acs.biomac.5b00999
Maysinger D, Gröger D, Lake A, Licha K, Weinhart M, Chang PKY et al. Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits. Biomacromolecules. 2015 Sep 14;16(9):3073-3082. Epub 2015 Aug 12. doi: 10.1021/acs.biomac.5b00999
Maysinger, Dusica ; Gröger, Dominic ; Lake, Andrew et al. / Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits. in: Biomacromolecules. 2015 ; Jahrgang 16, Nr. 9. S. 3073-3082.
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title = "Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits",
abstract = "Hyperactivity of microglia and loss of functional circuitry is a common feature of many neurological disorders including those induced or exacerbated by inflammation. Herein, we investigate the response of microglia and changes in hippocampal dendritic postsynaptic spines by dendritic polyglycerol sulfate (dPGS) treatment. Mouse microglia and organotypic hippocampal slices were exposed to dPGS and an inflammogen (lipopolysaccharides). Measurements of intracellular fluorescence and confocal microscopic analyses revealed that dPGS is avidly internalized by microglia but not CA1 pyramidal neurons. Concentration and time-dependent response studies consistently showed no obvious toxicity of dPGS. The adverse effects induced by proinflammogen LPS exposure were reduced and dendritic spine morphology was normalized with the addition of dPGS. This was accompanied by a significant reduction in nitrite and proinflammatory cytokines (TNF-α and IL-6) from hyperactive microglia suggesting normalized circuitry function with dPGS treatment. Collectively, these results suggest that dPGS acts anti-inflammatory, inhibits inflammation-induced degenerative changes in microglia phenotype and rescues dendritic spine morphology.",
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AU - Maysinger, Dusica

AU - Gröger, Dominic

AU - Lake, Andrew

AU - Licha, Kai

AU - Weinhart, Marie

AU - Chang, Philip K.Y.

AU - Mulvey, Rose

AU - Haag, Rainer

AU - McKinney, R. Anne

N1 - Publisher Copyright: © 2015 American Chemical Society.

PY - 2015/9/14

Y1 - 2015/9/14

N2 - Hyperactivity of microglia and loss of functional circuitry is a common feature of many neurological disorders including those induced or exacerbated by inflammation. Herein, we investigate the response of microglia and changes in hippocampal dendritic postsynaptic spines by dendritic polyglycerol sulfate (dPGS) treatment. Mouse microglia and organotypic hippocampal slices were exposed to dPGS and an inflammogen (lipopolysaccharides). Measurements of intracellular fluorescence and confocal microscopic analyses revealed that dPGS is avidly internalized by microglia but not CA1 pyramidal neurons. Concentration and time-dependent response studies consistently showed no obvious toxicity of dPGS. The adverse effects induced by proinflammogen LPS exposure were reduced and dendritic spine morphology was normalized with the addition of dPGS. This was accompanied by a significant reduction in nitrite and proinflammatory cytokines (TNF-α and IL-6) from hyperactive microglia suggesting normalized circuitry function with dPGS treatment. Collectively, these results suggest that dPGS acts anti-inflammatory, inhibits inflammation-induced degenerative changes in microglia phenotype and rescues dendritic spine morphology.

AB - Hyperactivity of microglia and loss of functional circuitry is a common feature of many neurological disorders including those induced or exacerbated by inflammation. Herein, we investigate the response of microglia and changes in hippocampal dendritic postsynaptic spines by dendritic polyglycerol sulfate (dPGS) treatment. Mouse microglia and organotypic hippocampal slices were exposed to dPGS and an inflammogen (lipopolysaccharides). Measurements of intracellular fluorescence and confocal microscopic analyses revealed that dPGS is avidly internalized by microglia but not CA1 pyramidal neurons. Concentration and time-dependent response studies consistently showed no obvious toxicity of dPGS. The adverse effects induced by proinflammogen LPS exposure were reduced and dendritic spine morphology was normalized with the addition of dPGS. This was accompanied by a significant reduction in nitrite and proinflammatory cytokines (TNF-α and IL-6) from hyperactive microglia suggesting normalized circuitry function with dPGS treatment. Collectively, these results suggest that dPGS acts anti-inflammatory, inhibits inflammation-induced degenerative changes in microglia phenotype and rescues dendritic spine morphology.

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