Antagonistic effects of melatonin on glutamate release and neurotoxicity in cerebral cortex.
OBJECTIVE
To observe the effects of melatonin (Mel) on glutamate (Glu) release from the cortical synaptosomes in old mice and on neurotoxicity induced by KCl, Glu in cultured cortical cells of fetal rat and to explore the antiaging mechanism of Mel.


METHODS
Glu release by the synaptosomes in old mouse cerebral cortex was detected in a spectrofluorophotometer. The neuronal viability in primary cultures from rat cerebral cortex was assessed using MTT stain and lactate dehydrogenase (LDH) efflux in the bathing medium.


RESULTS
Mel inhibited the K+ (30 mmol.L-1)-induced Glu release from synaptosomes either in calcium dependent or independent conditions [control (10.6 +/- 1.1), (9.2 +/- 0.7) mumol.g-1 (protein); Mel 0.1 mumol.L-1 (6.5 +/- 0.9), (7.5 +/- 0.6) mumol.g-1 (protein), respectively, P < 0.01 vs control group), increased MTT activity (control 0.67 +/- 0.04, 0.81 +/- 0.03; Mel 0.1 mumol.L-1 0.715 +/- 0.023, 0.925 +/- 0.027, P < 0.01 vs control group] and decreased LDH efflux (control 0.400 +/- 0.016, 0.379 +/- 0.016; Mel 0.1 mumol.L-1 0.345 +/- 0.021, 0.340 +/- 0.012, respectively, P < 0.01 vs control group), therefore, protected the neuronal viability against KCl and Glu-induced injury.


CONCLUSIONS
The inhibitory effect of Mel on Glu release from cortical synaptosome and the protective effect of Mel on cortical neurons against neurotoxicity are its antiaging mechanisms.
Zhang
Q Z
QZ
Second Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Gong
Y S
YS
Zhang
J T
JT
D000375:Aging / Q000187:drug effects*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism
D018696:Neuroprotective Agents; D018698:Glutamic Acid; D008550:Melatonin