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. 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.
Wisman
Liselijn A B
LA
Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands. L.A.BWisman@neuro.azu.nl
van Muiswinkel
Freek L
FL
de Graan
Pierre N E
PN
Hol
Elly M
EM
Bär
Peter R
PR
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002450:Cell Communication / Q000235:genetics*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D018920:Coculture Techniques; D003998:Dicarboxylic Acids / Q000494:pharmacology; D005818:Genetic Engineering; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D009046:Motor Neurons / Q000502:physiology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D003998:Dicarboxylic Acids; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D018698:Glutamic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid