ArticleThe international journal of neuropsychopharmacology2014
Melatonin attenuates memory impairment induced by Klotho gene deficiency via interactive signaling between MT2 receptor, ERK, and Nrf2-related antioxidant potential.
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23 citing papers in PubMed, 79 citations in OpenAlex.
- Efficacy of silicon-based agent against aging-related frailty.Scientific reports · 2026Article
- Reduced serum Klotho in chronic schizophrenia: diagnostic value and association with cognitive impairment.Frontiers in psychiatry · 2026Article
- Up-regulation of Oxidative Burden, NFκB, and D1 Receptor Is Involved in the Neuropsychotoxic Behaviors Induced by Camfetamine, a New Psychoactive Substance; Involvements of the Neuromodulation by GPx-1 Gene.Neurochemical research · 2025Article
- Insufficient Sleep and Alzheimer's Disease: Potential Approach for Therapeutic Treatment Methods.Brain sciences · 2024Review
- Melatonin attenuates scopolamine-induced cognitive dysfunction through SIRT1/IRE1α/XBP1 pathway.CNS neuroscience & therapeutics · 2024Article
- Association of Dietary Vitamin C Consumption with Serum Klotho Concentrations.Foods (Basel, Switzerland) · 2023Article
- Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsOMolecules (Basel, Switzerland) · 2021Article
- Melatonin Promotes In Vitro Maturation of Vitrified-Warmed Mouse Germinal Vesicle Oocytes, Potentially by Reducing Oxidative Stress through the Nrf2 Pathway.Animals : an open access journal from MDPI · 2021Article
- Article
- Novel Antioxidant, Deethylated Ethoxyquin, Protects against Carbon Tetrachloride Induced Hepatotoxicity in Rats by Inhibiting NLRP3 Inflammasome Activation and Apoptosis.Antioxidants (Basel, Switzerland) · 2021Article
- Melatonin Attenuates Sepsis-Induced Small-Intestine Injury by Upregulating SIRT3-Mediated Oxidative-Stress Inhibition, Mitochondrial Protection, and Autophagy Induction.Frontiers in immunology · 2021Article
- Melatonin Alleviates Acute Sleep Deprivation-Induced Memory Loss in Mice by Suppressing Hippocampal Ferroptosis.Frontiers in pharmacology · 2021Article
- The Role of Adaptogens in Prophylaxis and Treatment of Viral Respiratory Infections.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Increased Plasma Level of Longevity Protein Klotho as a Potential Indicator of Cognitive Function Preservation in Patients With Schizophrenia.Frontiers in neuroscience · 2020Article
- Epigenetic regulation of melatonin receptors in neuropsychiatric disorders.British journal of pharmacology · 2018Review
- Identification of a melatonin receptor type 1A gene (AccMTNR1A) in Apis cerana cerana and its possible involvement in the response to low temperature stress.Die Naturwissenschaften · 2018Article
- Comparing the Effects of Melatonin with Caloric Restriction in the Hippocampus of Aging Mice: Involvement of Sirtuin1 and the FOXOs Pathway.Neurochemical research · 2018Article
- Protective Potential of the Glutathione Peroxidase-1 Gene in Abnormal Behaviors Induced by Phencyclidine in Mice.Molecular neurobiology · 2017Article
- Melatonin attenuated the brain damage and cognitive impairment partially through MT2 melatonin receptor in mice with chronic cerebral hypoperfusion.Oncotarget · 2017Article
- YY-1224, a terpene trilactone-strengthened Ginkgo biloba, attenuates neurodegenerative changes induced by β-amyloid (1-42) or double transgenic overexpression of APP and PS1 via inhibition of cyclooxygenase-2.Journal of neuroinflammation · 2017Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Eun-Joo ShinNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Yoon Hee ChungNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Hoang-Lan Thi LeNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Ji Hoon JeongNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Duy-Khanh DangNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Yunsung NamNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Myung Bok WieNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Seung-Yeol NahNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Yo-Ichi NabeshimaNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Toshitaka NabeshimaNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Hyoung-Chun KimNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea (Drs Shin, Le, Dang, Nam, and Kim); Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Chung); Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea (Dr Jeong); School of Veterinary Medicine, Kangwon National University, Chunchon 200-701, Republic of Korea (Dr Wie); Ginseng Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea (Dr Nah); Laboratory of Molecular Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan (Dr Y-I Nabeshima); Department of Regional Pharmaceutical Care and Science, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan (Dr T Nabeshima).
Konkuk University · KRKangwon National University · KRMeijo University · JP
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe demonstrated that oxidative stress plays a crucial role in cognitive impairment in klotho mutant mice, a genetic model of aging. Since down-regulation of melatonin due to aging is well documented, we used this genetic model to determine whether the antioxidant property of melatonin affects memory impairment.
methodsFirst, we examined the effects of melatonin on hippocampal oxidative parameters and the glutathione/oxidized glutathione (GSH/GSSG) ratio and memory dysfunction of klotho mutant mice. Second, we investigated whether a specific melatonin receptor is involved in the melatonin-mediated pharmacological response by application with melatonin receptor antagonists. Third, we examined phospho-extracellular-signal-regulated kinase (ERK) expression, nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, Nrf2 DNA binding activity, and glutamate-cysteine ligase (GCL) mRNA expression. Finally, we examined effects of the ERK inhibitor SL327 in response to antioxidant efficacy and memory enhancement mediated by melatonin.
resultsTreatment with melatonin resulted in significant attenuations of oxidative damage, a decrease in the GSH/GSSG ratio, and a significant amelioration of memory impairment in this aging model. These effects of melatonin were significantly counteracted by the selective MT2 receptor antagonist 4-P-PDOT. Importantly, 4-P-PDOT or SL327 also counteracted melatonin-mediated attenuation in response to the decreases in phospho-ERK expression, Nrf2 nuclear translocation, Nrf2 DNA-binding activity, and GCL mRNA expression in the hippocampi of klotho mutant mice. SL327 also counteracted the up-regulation of the GSH/GSSG ratio and the memory enhancement mediated by melatonin in klotho mutant mice.
conclusionsMelatonin attenuates oxidative stress and the associated memory impairment induced by klotho deficiency via signaling interaction between the MT2 receptor and ERK- and Nrf2-related antioxidant potential.
Indexed as
AnimalsAntioxidantsBehavior, AnimalDisease Models, AnimalDose-Response Relationship, DrugExtracellular Signal-Regulated MAP KinasesGlucuronidaseGlutamate-Cysteine LigaseGlutathioneHippocampusKlotho ProteinsMelatoninMemoryMemory DisordersMice, Inbred C3HMice, KnockoutAntioxidantsExtracellular Signal-Regulated MAP KinasesGlucuronidaseGlutamate-Cysteine LigaseGlutathioneKlotho ProteinsMelatoninNfe2l2 protein, mouseNF-E2-Related Factor 2Nootropic AgentsProtein Kinase InhibitorsReceptor, Melatonin, MT2hippocampusKlotho mutant micemelatonin MT2 receptor/ERK/Nrf2memoryoxidative stress
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