Cells over-expressing EAAT2 protect motoneurons from excitotoxic death in vitro

Amyotrophic lateral sclerosis is an incurable disease in which cerebral and spinal motoneurons degenerate, causing paralysis and death within 2–5 years. One of the pathogenic factors of motoneuron death is a chronic excess of glutamate, which exceeds its removal by astrocytes, i.e. excitotoxicity. E...

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Veröffentlicht in:Neuroreport 2003-10, Vol.14 (15), p.1967-1970
Hauptverfasser: Wisman, Liselijn A. B, van Muiswinkel, Freek L, de Graan, Pierre N. E, Hol, Elly M, Bär, Peter R
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container_end_page 1970
container_issue 15
container_start_page 1967
container_title Neuroreport
container_volume 14
creator Wisman, Liselijn A. B
van Muiswinkel, Freek L
de Graan, Pierre N. E
Hol, Elly M
Bär, Peter R
description Amyotrophic lateral sclerosis is an incurable disease in which cerebral and spinal motoneurons degenerate, causing paralysis and death within 2–5 years. One of the pathogenic factors of motoneuron death is a chronic excess of glutamate, which exceeds its removal by astrocytes, i.e. excitotoxicity. Extra glutamate uptake in the spinal cord may slow down or prevent motoneuron death. We have engineered cells over-expressing the main glutamate transporter and tested their potential to rescue motoneurons exposed to high levels of glutamate in vitro. The engineered cells protected motoneurons in a motoneuron–astrocyte co-culture at glutamate concentrations when astrocytes were no longer capable of removing glutamate. This suggests that engineered cells, introduced into the spinal column, can help remove glutamate, thereby preventing motoneuron death.
doi_str_mv 10.1097/00001756-200310270-00017
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source MEDLINE; Journals@Ovid Complete
subjects Animals
Astrocytes - drug effects
Astrocytes - metabolism
Biological and medical sciences
Blotting, Western
Cell Communication - genetics
Cell Death - drug effects
Cell Death - genetics
Coculture Techniques
Dicarboxylic Acids - pharmacology
Fundamental and applied biological sciences. Psychology
Genetic Engineering
Glutamic Acid - metabolism
Glutamic Acid - toxicity
Humans
Motor Neurons - physiology
Neurotransmitter Uptake Inhibitors - pharmacology
Pyrrolidines - pharmacology
Rats
Rats, Sprague-Dawley
Vertebrates: nervous system and sense organs
title Cells over-expressing EAAT2 protect motoneurons from excitotoxic death in vitro
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