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 (t...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2003-02, Vol.20 (1), p.53-60
Main Authors: Mir, Cecilia, Clotet, Josep, Aledo, Rosa, Durany, Núria, Argemí, Josep, Lozano, Rafael, Cervós-Navarro, Jordi, Casals, Núria
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Brain Ischemia - drug therapy
Brain Ischemia - metabolism
Brain Ischemia - physiopathology
Cells
Cells, Cultured
Cerebellar Cortex - drug effects
Cerebellar Cortex - metabolism
Cerebellar Cortex - physiopathology
Cytidine Diphosphate Choline - pharmacology
Cytidine Diphosphate Choline - therapeutic use
Dose-Response Relationship, Drug
Drug Combinations
Drug Interactions - physiology
Excitatory Amino Acid Antagonists - pharmacology
Excitatory Amino Acid Antagonists - therapeutic use
Glutamic Acid - metabolism
Glutamic Acid - toxicity
L-Lactate Dehydrogenase
Neurodegenerative Diseases - drug therapy
Neurodegenerative Diseases - metabolism
Neurodegenerative Diseases - physiopathology
Neurons - drug effects
Neurons - metabolism
Neuroprotective Agents - pharmacology
Neuroprotective Agents - toxicity
Neurotoxins - antagonists & inhibitors
Rats
Rats, Sprague-Dawley
Rodents
Time Factors
Trypan Blue
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Summary: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.
ISSN:0895-8696
1559-1166
0895-8696
DOI:10.1385/JMN:20:1:53