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Antagonistic effects of melatonin on glutamate release and neurotoxicity in cerebral cortex
Q Z Zhang1, Y S Gong, J T Zhang
1Second Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Aim:
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.
Conclusion:
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.
Insights
Melatonin (Mel) reduces glutamate release from brain cells and protects neurons from damage. These findings suggest Melatonin
Area of Science:
- Neuroscience
- Gerontology
- Biochemistry
Background:
- Aging is associated with increased glutamate release and neuronal vulnerability.
- Melatonin is a hormone with known antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the effects of melatonin on glutamate release in aged mice.
- To evaluate melatonin's neuroprotective capacity against excitotoxicity in vitro.
- To elucidate the anti-aging mechanisms of melatonin.
Main Methods:
- Glutamate release from cortical synaptosomes of old mice was measured using spectrofluorophotometry.
- Neuronal viability in primary rat cortical cell cultures was assessed via MTT assay and lactate dehydrogenase (LDH) efflux.
- Potassium chloride (KCl) and glutamate (Glu) were used to induce excitotoxicity.
Main Results:
- Melatonin significantly inhibited KCl-induced glutamate release from synaptosomes in both calcium-dependent and independent conditions.
- Melatonin treatment increased MTT activity, indicating enhanced neuronal viability.
- Melatonin reduced LDH efflux, suggesting decreased neuronal damage.
Conclusions:
- Melatonin's inhibition of glutamate release from cortical synaptosomes is a key anti-aging mechanism.
- Melatonin confers neuroprotection against excitotoxicity, contributing to its anti-aging effects.