Details
| Original language | English |
|---|---|
| Pages (from-to) | 3073-3082 |
| Number of pages | 10 |
| Journal | Biomacromolecules |
| Volume | 16 |
| Issue number | 9 |
| Early online date | 12 Aug 2015 |
| Publication status | Published - 14 Sept 2015 |
| Externally published | Yes |
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 subject areas
- Chemical Engineering(all)
- Bioengineering
- Materials Science(all)
- Biomaterials
- Materials Science(all)
- Polymers and Plastics
- Materials Science(all)
- Materials Chemistry
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In: Biomacromolecules, Vol. 16, No. 9, 14.09.2015, p. 3073-3082.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits
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.
UR - http://www.scopus.com/inward/record.url?scp=84941337267&partnerID=8YFLogxK
U2 - 10.1021/acs.biomac.5b00999
DO - 10.1021/acs.biomac.5b00999
M3 - Article
C2 - 26218295
AN - SCOPUS:84941337267
VL - 16
SP - 3073
EP - 3082
JO - Biomacromolecules
JF - Biomacromolecules
SN - 1525-7797
IS - 9
ER -