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      • Delivery of pineal melatonin to the brain and SCN: role of canaliculi, cerebrospinal fluid, tanycytes and Virchow-Robin perivascular spaces.

        Reiter, Russel J,Tan, Dun Xian,Kim, Seok Joong,Cruz, Maria Helena C Springer Science + Business Media 2014 BRAIN STRUCTURE AND FUNCTION Vol.219 No.6

        <P>Historically, the direct release of pineal melatonin into the capillary bed within the gland has been accepted as the primary route of secretion. Herein, we propose that the major route of melatonin delivery to the brain is after its direct release into the cerebrospinal fluid (CSF) of the third ventricle (3V). Melatonin concentrations in the CSF are not only much higher than in the blood, also, there is a rapid nocturnal rise at darkness onset and precipitous decline of melatonin levels at the time of lights on. Because melatonin is a potent free radical scavenger and antioxidant, we surmise that the elevated CSF levels are necessary to combat the massive free radical damage that the brain would normally endure because of its high utilization of oxygen, the parent molecule of many toxic oxygen metabolites, i.e., free radicals. Additionally, the precise rhythm of CSF melatonin provides the master circadian clock, the suprachiasmatic nucleus, with highly accurate chronobiotic information regarding the duration of the dark period. We predict that the discharge of melatonin directly into the 3V is aided by a number of epithalamic structures that have heretofore been overlooked; these include interpinealocyte canaliculi and evaginations of the posterodorsal 3V that directly abut the pineal. Moreover, the presence of tanycytes in the pineal recess and/or a discontinuous ependymal lining in the pineal recess allows melatonin ready access to the CSF. From the ventricles melatonin enters the brain by diffusion and by transport through tanycytes. Melatonin-rich CSF also circulates through the aqueduct and eventually into the subarachnoid space. From the subarachnoid space surrounding the brain, melatonin penetrates into the deepest portions of the neural tissue via the Virchow-Robin perivascular spaces from where it diffuses into the neural parenchyma. Because of the high level of pineal-derived melatonin in the CSF, all portions of the brain are better shielded from oxidative stress resulting from toxic oxygen derivatives.</P>

      • KCI등재후보

        Melatonin improves antioxidant defense mechanism of basil under drought stress

        Naghizadeh Mehdi,Reiter Russel J.,Kabiri Rozita,Moradi Rooholla 한국원예학회 2024 Horticulture, Environment, and Biotechnology Vol.65 No.1

        Basil ( Ocimum basilicum L.) is a highly important medicinal plant. In this study, the interactional eff ects of water defi cit and melatonin application on growth and physio-biochemical characteristics of basil were investigated. The treatments included three levels of irrigation (100, 75 and 50% of fi eld capacity) and three melatonin concentrations (0, 50 and 100 μmol). Drought stress decreased the dry weight of plants but application of 100 μmol melatonin markedly increased dry weight under these conditions. Melatonin profoundly enhanced plant drought tolerance by stimulating the antioxidant enzymes (catalase, phenylalanine ammonia-lyase, ascorbate peroxidase and polyphenol oxidase) activities and secondary metabolites (total phenol, fl avonoid and anthocyanin contents). Furthermore, melatonin application reduced lipid peroxi dation and increased the relative water content and photosynthetic pigments, resulting in an improvement of plant dry matter. It is concluded that foliar spraying with melatonin induced the pre-adaptive responses to drought stress followed by regulating antioxidant defense mechanisms.

      • Melatonin plus exercise-based neurorehabilitative therapy for spinal cord injury

        Hong, Yonggeun,Palaksha, K. J.,Park, Kanghui,Park, Sookyoung,Kim, Hyun-Dong,Reiter, Russel J.,Chang, Kyu-Tae Blackwell Publishing Ltd 2010 Journal of pineal research Vol.49 No.3

        <P>Abstract: </P><P>Spinal cord injury (SCI) is damage to the spinal cord caused by the trauma or disease that results in compromised or loss of body function. Subsequent to SCI in humans, many individuals have residual motor and sensory deficits that impair functional performance and quality of life. The available treatments for SCI are rehabilitation therapy, activity-based therapies, and pharmacological treatment using antioxidants and their agonists. Among pharmacological treatments, the most efficient and commonly used antioxidant for experimental SCI treatment is melatonin, an indolamine secreted by pineal gland at night. Melatonin’s receptor-independent free radical scavenging action and its broad-spectrum antioxidant activity makes it an ideal antioxidant to protect tissue from oxidative stress-induced secondary damage after SCI. Owing to the limitations of an activity-based therapy and antioxidant treatment singly on the functional recovery and oxidative stress-induced secondary damages after SCI, a melatonin plus exercise treatment may be a more effective therapy for SCI. As suggested herein, supplementation with melatonin in conjunction with exercise not only would improve the functional recovery by enhancing the beneficial effects of exercise but would reduce the secondary tissue damage simultaneously. Finally, melatonin may protect against exercise-induced fatigue and impairments. In this review, based on the documented evidence regarding the beneficial effects of melatonin, activity-based therapy and the combination of both on functional recovery, as well as reduction of secondary damage caused by oxidative stress after SCI, we suggest the melatonin combined with exercise would be a novel neurorehabilitative strategy for the faster recovery after SCI.</P>

      • Fundamental Issues Related to the Origin of Melatonin and Melatonin Isomers during Evolution: Relation to Their Biological Functions

        Tan, Dun-Xian,Zheng, Xiaodong,Kong, Jin,Manchester, Lucien C.,Hardeland, Ruediger,Kim, Seok Joong,Xu, Xiaoying,Reiter, Russel J. MDPI 2014 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.15 No.9

        <P>Melatonin and melatonin isomers exist and/or coexist in living organisms including yeasts, bacteria and plants. The levels of melatonin isomers are significantly higher than that of melatonin in some plants and in several fermented products such as in wine and bread. Currently, there are no reports documenting the presence of melatonin isomers in vertebrates. From an evolutionary point of view, it is unlikely that melatonin isomers do not exist in vertebrates. On the other hand, large quantities of the microbial flora exist in the gut of the vertebrates. These microorganisms frequently exchange materials with the host. Melatonin isomers, which are produced by these organisms inevitably enter the host’s system. The origins of melatonin and its isomers can be traced back to photosynthetic bacteria and other primitive unicellular organisms. Since some of these bacteria are believed to be the precursors of mitochondria and chloroplasts these cellular organelles may be the primary sites of melatonin production in animals or in plants, respectively. Phylogenic analysis based on its rate-limiting synthetic enzyme, serotonin <I>N</I>-acetyltransferase (SNAT), indicates its multiple origins during evolution. Therefore, it is likely that melatonin and its isomer are also present in the domain of archaea, which perhaps require these molecules to protect them against hostile environments including extremely high or low temperature. Evidence indicates that the initial and primary function of melatonin and its isomers was to serve as the first-line of defence against oxidative stress and all other functions were acquired during evolution either by the process of adoption or by the extension of its antioxidative capacity.</P>

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