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• W1987338717 endingPage "1886" @default.
• W1987338717 startingPage "1879" @default.
• W1987338717 abstract "Conflicting results have been reported concerning the toxicity of cerebrospinal fluid from patients with amyotrophic lateral sclerosis (ALS-CSF) when added to neuronal cultures. The possible toxic factor(s) and the exact mode of action (e.g. requirement of glial cells) have not been identified so far. Glutamate is a potential candidate for this toxic effect, since antagonists of ionotropic glutamate receptors have been shown to attenuate ALS-CSF toxicity. We studied the effects of ALS-CSF on mixed and motoneuron-enriched chick embryonic spinal cord cultures. We found a toxic action of ALS-CSF in both culture types which could not be attenuated by 5 kDa-filtration or 15 min 90 °C heating. Nevertheless, the metabotropic glutamate receptor (mGluR) group I antagonist 1-aminoindan-1,5-dicarboxylic acid, but also the group I agonist (s)-3,5-dihydroxyphenylglycine (DHPG) exerted protective effects against ALS-CSF toxicity. In this experimental setting, DHPG may functionally act via a receptor blockade due to sustained activation. No protective effect was seen with the mGluR group III inhibitor (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG). Addition of DHPG did not increase the protective action of the AMPA inhibitor 6-chloro-4-hydroxyquinoline-2-carboxylic acid (6-CKU). Addition of l-glutamate did not mimic these toxic ALS-CSF effects in motoneuron-enriched cultures. Our experiments demonstrate that ALS-CSF toxicity is mediated by a small heat-resistant molecule which may act directly on neurons. Since blockade of group I mGluRs exerts a protective effect, the possibility of targeting these mGluRs pharmacologically in motoneuron disease should be kept in mind." @default.
• W1987338717 created "2016-06-24" @default.
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• W1987338717 creator A5055801479 @default.
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• W1987338717 date "2006-01-01" @default.
• W1987338717 modified "2023-10-14" @default.
• W1987338717 title "Protective effect of metabotropic glutamate receptor inhibition on amyotrophic lateral sclerosis–cerebrospinal fluid toxicity in vitro" @default.
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• W1987338717 doi "https://doi.org/10.1016/j.neuroscience.2006.05.044" @default.
• W1987338717 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16820266" @default.
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