Neuroprotective Effect of Melatonin against Kainic Acid-Induced Oxidative Injury in Hippocampal Slice Culture of Rats

Kim, Hyung A; Lee, Kyung Hee; Lee, Bae Hwan

doi:10.3390/ijms15045940

Cited by 16 publications

(11 citation statements)

References 34 publications

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“…It has been well-documented, as discussed above, that melatonin and resveratrol both exert neuroprotective activity against cognitive deficits via the inhibition of elevated proinflammatory cytokines. It has been shown that melatonin and resveratrol inhibit NF-κB activation and restrain microglia activation, which further reduces the production of proinflammatory cytokines [63][64][65] . In our study, we found that melatonin and resveratrol inhibited the elevated proinflammatory cytokines in the hippocampus of BCCAO-treated rats.…”

Section: Discussionmentioning

confidence: 99%

Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal Damage in a Rat Model of Vascular Dementia

Shen¹,

Tian²,

Sang³

et al. 2016

Neuroimmunomodulation

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Objectives: This study was intended to investigate whether treatment with resveratrol and melatonin alone or in combination can exert neurorestorative effects in a rat model of vascular dementia. Methods: Briefly, male Wistar rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) by surgery. After 4 weeks, the cognitive deficits were assessed using the Morris water maze and novel object recognition tests. The biochemical parameters of oxidative stress and inflammation were also assessed. Results: Rats in the BCCAO group showed cognitive deficits, accompanied by oxidonitrosative stress, neuroinflammation, and a reduction in brain-derived neurotrophic factor (BDNF) in the hippocampus region. Moreover, the acetylcholinesterase activity in the hippocampus was found to be increased in the BCCAO group compared to the sham group. The 4-week treatment with melatonin (10 mg/kg) and resveratrol (20 mg/kg) alone and in combination (melatonin 5 mg/kg and reseveratrol 10 mg/kg) caused a significant improvement in the cognitive deficits induced by BCCAO, accompanied by a reversal of oxidonitrosative stress, neuroinflammation, and BDNF depletion in the hippocampus region. Additionally, the treatment with melatonin and resveratrol significantly decreased acetylcholinesterase activity compared to in the BCCAO group. Melatonin and resveratrol ameliorated the BDNF expression of hippocampal protein. Conclusion: These results emphasize that coadministration of melatonin and resveratrol can be beneficial in BCCAO-induced vascular dementia through changes in BDNF expressions.

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Section: Discussionmentioning

confidence: 99%

Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal Damage in a Rat Model of Vascular Dementia

Shen¹,

Tian²,

Sang³

et al. 2016

Neuroimmunomodulation

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“…Excitotoxic conditions have been implicated in acute and chronic neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and epilepsy [3]. In animal models of excitotoxic neurodegeneration, chemical convulsants such as kainic acid (KA) have been utilized to mimic pathological conditions observed in patients [4,5]. KA is a neurotoxic analogue of glutamate that binds to kainate receptors, resulting in overstimulation of neurons at high doses [6].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection from Excitotoxic Injury by Local Administration of Lipid Emulsion into the Brain of Rats

Tanioka

Park

Shim

et al. 2020

IJMS

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Lipid emulsion was recently shown to attenuate cell death caused by excitotoxic conditions in the heart. There are key similarities between neurons and cardiomyocytes, such as excitability and conductibility, which yield vulnerability to excitotoxic conditions. However, systematic investigations on the protective effects of lipid emulsion in the central nervous system are still lacking. This study aimed to determine the neuroprotective effects of lipid emulsion in an in vivo rat model of kainic acid-induced excitotoxicity through intrahippocampal microinjections. Kainic acid and/or lipid emulsion-injected rats were subjected to the passive avoidance test and elevated plus maze for behavioral assessment. Rats were sacrificed at 24 h and 72 h after kainic acid injections for molecular study, including immunoblotting and qPCR. Brains were also cryosectioned for morphological analysis through cresyl violet staining and Fluorojade-C staining. Anxiety and memory functions were significantly preserved in 1% lipid emulsion-treated rats. Lipid emulsion was dose-dependent on the protein expression of β-catenin and the phosphorylation of GSK3-β and Akt. Wnt1 mRNA expression was elevated in lipid emulsion-treated rats compared to the vehicle. Neurodegeneration was significantly reduced mainly in the CA1 region with increased cell survival. Our results suggest that lipid emulsion has neuroprotective effects against excitotoxic conditions in the brain and may provide new insight into its potential therapeutic utility.

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“…It catalyzes the production of leukotrienes (LTs) and reactive oxygen species (ROS) from arachidonic acid 19 , 20 . ALOX5 is known to be involved in various physiological and pathological processes, including oxidative stress response, inflammation and cancer 21 – 25 . It was reported previously that loss of Alox5 impairs the function of leukemic stem cells (LSCs) in BCR-ABL -induced chronic myelogenous leukemia (CML) 26 .…”

Section: Introductionmentioning

confidence: 99%

ALOX5 exhibits anti-tumor and drug-sensitizing effects in MLL-rearranged leukemia

Wang

Skibbe

et al. 2017

Sci Rep

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MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high rate of relapse and therapeutic failure due to chemotherapy resistance. In analysis of our Affymetrix microarray profiling and chromatin immunoprecipitation (ChIP) assays, we found that ALOX5 is especially down-regulated in MLL-rearranged AML, via transcription repression mediated by Polycomb repressive complex 2 (PRC2). Colony forming/replating and bone marrow transplantation (BMT) assays showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in vivo. Strikingly, leukemic cells with Alox5 overexpression showed a significantly higher sensitivity to the standard chemotherapeutic agents, i.e., doxorubicin (DOX) and cytarabine (Ara-C). The drug-sensitizing role of Alox5 was further confirmed in human and murine MLL-rearranged AML cell models in vitro, as well as in the in vivo MLL-rearranged AML BMT model coupled with treatment of “5 + 3” (i.e. DOX plus Ara-C) regimen. Stat and K-Ras signaling pathways were negatively correlated with Alox5 overexpression in MLL-AF9-leukemic blast cells; inhibition of the above signaling pathways mimicked the drug-sensitizing effect of ALOX5 in AML cells. Collectively, our work shows that ALOX5 plays a moderate anti-tumor role and functions as a drug sensitizer, with a therapeutic potential, in MLL-rearranged AML.

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Neuroprotective Effect of Melatonin against Kainic Acid-Induced Oxidative Injury in Hippocampal Slice Culture of Rats

Cited by 16 publications

References 34 publications

Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal Damage in a Rat Model of Vascular Dementia

Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal Damage in a Rat Model of Vascular Dementia

Neuroprotection from Excitotoxic Injury by Local Administration of Lipid Emulsion into the Brain of Rats

ALOX5 exhibits anti-tumor and drug-sensitizing effects in MLL-rearranged leukemia

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