CDP-choline prevents glutamate-mediated cell death in cerebellar granule neurons.
Cytidine 5'-diphosphocholine (CDP-choline) has been shown to reduce neuronal degeneration induced in central nervous system (CNS) injury. However, the precise mechanism underlying the neuroprotective properties of this molecule is still unknown. Excitotoxicity causes cell death in CNS injury (trauma or ischemia) and has also been involved in neurodegenerative diseases. We have examined whether CDP-choline prevents glutamate-mediated cell death, determined by trypan blue exclusion and lactate dehydrogenase activity assays. Pretreatment of rat cerebellar granule cells (CGCs) with CDP-choline causes a dose- and time-dependent reduction of glutamate-induced excitotoxicity. Cell death is prevented >50% when 100 microM CDP-choline is added 6 d before the glutamate excitotoxic insult but less than 20% when added concomitantly with glutamate. Pretreatment of CGCs with CDP-choline reduces almost completely (>80%) the number of apoptotic cells analyzed by flow cytometry, suggesting that CDP-choline exerts a neuroprotective effect by inhibiting the apoptotic pathway induced by glutamate.
Mir
Cecilia
C
Unit of Molecular and Cellular Biology, Faculty of Health Sciences, International University of Catalonia, Barcelona, Spain.
Clotet
Josep
J
Aledo
Rosa
R
Durany
Núria
N
Argemí
Josep
J
Lozano
Rafael
R
Cervós-Navarro
Jordi
J
Casals
Núria
N
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity; D007770:L-Lactate Dehydrogenase; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000633:toxicity; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014343:Trypan Blue
D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018698:Glutamic Acid; D003566:Cytidine Diphosphate Choline; D007770:L-Lactate Dehydrogenase; D014343:Trypan Blue