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The antioxidant melatonin reduces cortical neuronal death after intrastriatal injection of kainate in the rat.
Exp Brain Res. 1999 Jan; 124(2):241-7.EB

Abstract

The anti-excitotoxic efficacy of the pineal hormone melatonin was investigated in kainate-injured brains of rats. Kainate (a glutamate-receptor agonist, 2.5 nmol in 1 microl) was directly injected to unilateral striatum. Melatonin (10 mg/kg) was administrated intraperitoneally 1 h before and 1, 3, and 5 h after intrastriatal kainate injection in adult Sprague-Dawley rats. Three days after kainate injection, a significant neuronal damage was found, as determined by Nissl staining and the TUNEL method, not only in the injected striatum, but also in the ipsilateral neighboring cortex. The kainate-induced cortical apoptotic neuronal death was significantly attenuated by treatment with melatonin compared with the vehicle control group. However, no detectable changes were observed in the contralateral side of the brain in either vehicle- or melatonin-treated rats. Moreover, the biochemical results indicated that kainate can indeed induce oxidative stress, such as a decrease in the content of total glutathione (GSH), oxidized glutathione (GSSG), and an increase in the ratio of GSSG/GSH in the striatum and cortex compared with the contralateral brain regions. In the kainate-injected striatum, melatonin did not reduce the oxidative stress, but in the neighborhood of injected area-cortex, kainate-induced oxidative stress was significantly reduced by melatonin. Enhancement of glutathione-peroxidase activity was induced by intrastriatal kainate injection, not only in the cortical area of control and melatonin-treated rats, but also in striatum of control rats. However, a large elevation was found in the melatonin-treated cortex. Taking the morphological and biochemical data together, the present results suggest that melatonin functions as an antioxidant by upregulating the glutathione antioxidative defense system, thereby reducing neuronal death caused by excitotoxicity and preventing the kainate-induced damage from spreading to adjacent brain regions.

Authors+Show Affiliations

Chen ST
Department of Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Chuang JI
No affiliation info available

MeSH

AnimalsAntioxidantsApoptosisCerebral CortexCorpus StriatumExcitatory Amino Acid AgonistsGlutathioneGlutathione PeroxidaseIn Situ Nick-End LabelingKainic AcidMaleMelatoninNerve DegenerationNeuronsNeurotoxinsRatsRats, Sprague-Dawley

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9928847

Citation

Chen, S T., and J I. Chuang. "The Antioxidant Melatonin Reduces Cortical Neuronal Death After Intrastriatal Injection of Kainate in the Rat." Experimental Brain Research, vol. 124, no. 2, 1999, pp. 241-7.
Chen ST, Chuang JI. The antioxidant melatonin reduces cortical neuronal death after intrastriatal injection of kainate in the rat. Exp Brain Res. 1999;124(2):241-7.
Chen, S. T., & Chuang, J. I. (1999). The antioxidant melatonin reduces cortical neuronal death after intrastriatal injection of kainate in the rat. Experimental Brain Research, 124(2), 241-7.
Chen ST, Chuang JI. The Antioxidant Melatonin Reduces Cortical Neuronal Death After Intrastriatal Injection of Kainate in the Rat. Exp Brain Res. 1999;124(2):241-7. PubMed PMID: 9928847.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The antioxidant melatonin reduces cortical neuronal death after intrastriatal injection of kainate in the rat. AU - Chen,S T, AU - Chuang,J I, PY - 1999/2/3/pubmed PY - 1999/2/3/medline PY - 1999/2/3/entrez SP - 241 EP - 7 JF - Experimental brain research JO - Exp Brain Res VL - 124 IS - 2 N2 - The anti-excitotoxic efficacy of the pineal hormone melatonin was investigated in kainate-injured brains of rats. Kainate (a glutamate-receptor agonist, 2.5 nmol in 1 microl) was directly injected to unilateral striatum. Melatonin (10 mg/kg) was administrated intraperitoneally 1 h before and 1, 3, and 5 h after intrastriatal kainate injection in adult Sprague-Dawley rats. Three days after kainate injection, a significant neuronal damage was found, as determined by Nissl staining and the TUNEL method, not only in the injected striatum, but also in the ipsilateral neighboring cortex. The kainate-induced cortical apoptotic neuronal death was significantly attenuated by treatment with melatonin compared with the vehicle control group. However, no detectable changes were observed in the contralateral side of the brain in either vehicle- or melatonin-treated rats. Moreover, the biochemical results indicated that kainate can indeed induce oxidative stress, such as a decrease in the content of total glutathione (GSH), oxidized glutathione (GSSG), and an increase in the ratio of GSSG/GSH in the striatum and cortex compared with the contralateral brain regions. In the kainate-injected striatum, melatonin did not reduce the oxidative stress, but in the neighborhood of injected area-cortex, kainate-induced oxidative stress was significantly reduced by melatonin. Enhancement of glutathione-peroxidase activity was induced by intrastriatal kainate injection, not only in the cortical area of control and melatonin-treated rats, but also in striatum of control rats. However, a large elevation was found in the melatonin-treated cortex. Taking the morphological and biochemical data together, the present results suggest that melatonin functions as an antioxidant by upregulating the glutathione antioxidative defense system, thereby reducing neuronal death caused by excitotoxicity and preventing the kainate-induced damage from spreading to adjacent brain regions. SN - 0014-4819 UR - https://www.unboundmedicine.com/medline/citation/9928847/The_antioxidant_melatonin_reduces_cortical_neuronal_death_after_intrastriatal_injection_of_kainate_in_the_rat_ L2 - https://dx.doi.org/10.1007/s002210050619 DB - PRIME DP - Unbound Medicine ER -