NMDA-stimulated expression of BDNF mRNA in cultured cerebellar granule neurones.
The brain-derived neurotrophic factor (BDNF) affects the developing cerebellar granule cells. Exposure of 9-11-day-old primary cultures of rat cerebellar granule neurones for 3 h to a more depolarizing medium (additional 15-30 mM KCl) stimulated the release of glutamate and increased the BDNF mRNAs levels. This BDNF and mRNA upregulation was inhibited by dizocilpine (MK-801), the noncompetitive blocker of N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors, and mimicked by NMDA. Continuous (up to 5 h) culture exposure to non-toxic NMDA concentration resulted in a prolonged increase in BDNF mRNA expression and enhanced neuronal resistance to glutamate toxicity. The latter effect of NMDA was attenuated by cycloheximide, a protein synthesis inhibitor. The mechanisms responsible for NMDA-triggered BDNF upregulation and neuroprotection might be important in the compensatory response of brain to excitotoxicity.
Favaron
M
M
Fidia Research Laboratories, Abano Terme, Italy.
Manev
R M
RM
Rimland
J M
JM
Candeo
P
P
Beccaro
M
M
Manev
H
H
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D016202:N-Methylaspartate / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D019208:Brain-Derived Neurotrophic Factor; D005971:Glutamates; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D018698:Glutamic Acid; D016202:N-Methylaspartate; D011189:Potassium Chloride; D016291:Dizocilpine Maleate; D003513:Cycloheximide