Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK Interactions.

Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK Interactions. Research Abstract Details 

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Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK Interactions. Abstract Text:

Linda M Chicoine,Ben A Bahr,

Growing numbers of studies indicate that polysaccharides influence signaling events important for brain function. It has been speculated that such polysaccharide modulation of neuronal signals can promote synaptogenesis and cell maintenance. Here, we tested whether dextran sulfate, a polyanion that mimics natural mucopolysaccharides, protects hippocampal neurons against excitotoxic insults. An excitotoxin was applied to primary hippocampal cultures in the absence or presence of a large 500-kDa dextran sulfate (DS-L), a smaller 5-8-kDa species (DS-S), or sulfate-free dextran of 500 kDa. Only DS-L prevented neuronal damage as determined by a membrane permeability assay and phase contrast morphology. The sulfate and size dependence is also characteristic of DS-L's modulatory action on the channel activity of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors. The extent of neuroprotection correlates with the level of modulation of AMPA responses, and DS-L exhibits comparable EC(50) values for the two effects (3-7 nM). DS-L also modulates the link between AMPA receptors and mitogen-activated protein kinase (MAPK) involving extracellular signal-regulated protein kinase (ERK), well known for its involvement in cell survival and repair. Correspondingly, protection against N-methyl-D-aspartate (NMDA) excitotoxicity was evident in hippocampal slice cultures when DS-L was applied 30 min postinsult. These findings suggest that polysaccharides elicit neuroprotection in the brain, including enhanced repair responses through the AMPA receptor-MAPK axis.

Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK Interactions. Publishing Authors By Initials

LM Chicoine,BA Bahr,

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Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK Interactions. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of neuroscience research

VOLUME: 85

Page Numbers: 294-302

Journal Abbreviation: J. Neurosci. Res.

ISSN: 0360-4012

DAY: 1

MONTH: Feb

YEAR: 2007

Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK Interactions. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7600111

Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK Interactions. Keywords Mesh Terms:

KEYWORDS: alpha-Amino-3-hydroxy-5-methyl-4-isoxazo

MESH TERMS: metabolism

Chemical & Substance for Abstract: Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK Interactions. Information

Substance Name: Mitogen-Activated Protein Kinase Kinases

Registry Number: EC 2.7.1.-

Grant and Affiliation Information for Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK Interactions.

AFFILIATION: Cognetix, Inc., Salt Lake City, Utah, USA.

Country: United States

AGENCY: United States NINDS

GRANT: 1R43NS38404-01

ACRONYM: NS

MEDLINETA: J Neurosci Res

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