Melatonin inhibits cytosolic mitochondrial-DNA induced neuroinflammatory signaling in accelerated aging and neurodegeneration (original) (raw)
Related papers
Neuroimmunoendocrine system and mitochondria interplay in neurodegeneration: a role for melatonin
Structural and functional alterations of mitochondria are intimately linked to a wide variety of medical conditions. Many factors are involved in the regulation of mitochondrial function, including cytokines, chaperones, chemokines, neurosteroids, ubiquitins. The role of diffusely located cells of the neuroendocrine system, including biogenic amines and peptide hormones, in the regulation of mitochondrial function, as well as the role of altered mitochondrial function on these cells and system, awaits clarification. The current article looks at the interactions among the cells of the neuronal-glia, immune and endocrine systems, the diffuse neuroimmunoendocrine system (DNIES), and how DNIES interacts with mitochondrial function. Whilst changes in DNIES can impact on mitochondrial function, local and systemic alterations in mitochondrial function can alter the component systems of DNIES and their interactions. This has etiological, course and treatment implications for a wide range of medical conditions, including neurodegenerative disorders. Available data on the role for melatonin are reviewed and directions for future research are indicated.
The Role of Mitochondria in Brain Aging and the Effects of Melatonin
Current Neuropharmacology, 2010
Melatonin is an endogenous indoleamine present in different tissues, cellular compartments and organelles including mitochondria. When melatonin is administered orally, it is readily available to the brain where it counteracts different processes that occur during aging and age-related neurodegenerative disorders. These aging processes include oxidative stress and oxidative damage, chronic and acute inflammation, mitochondrial dysfunction and loss of neural regeneration. This review summarizes age related changes in the brain and the importance of oxidative/nitrosative stress and mitochondrial dysfunction in brain aging. The data and mechanisms of action of melatonin in relation to aging of the brain are reviewed as well.
Structural and functional alterations of mitochondria are intimately linked to a wide array of medical conditions. Many factors are involved in the regulation of mitochondrial function, including cytokines, chaperones, chemokines, neurosteroids, and ubiquitins. The role of diffusely located cells of the neuroendocrine system, including biogenic amines and peptide hormones, in the management of mitochondrial function, as well as the role of altered mitochondrial function in the regulation of these cells and system, is an area of intense investigation. The current article looks at the interactions among the cells of the neuronal-glia, immune and endocrine systems, namely the diffuse neuroimmunoendocrine system (DNIES), and how DNIES interacts with mitochondrial function. Whilst changes in DNIES can impact on mitochondrial function, local and systemic alterations in mitochondrial function can alter the component systems of DNIES and their interactions. This has etiological, course and treatment implications for a wide range of medical conditions, including neurodegenerative disorders. Available data on the role of melatonin in these interactions, at cellular and system levels, are reviewed, with directions for future research indicated.
Journal of Pineal Research, 2008
Abstract: Senescence-accelerated mice (SAMP8) and senescence-accelerated resistant mice (SAMR1) were studied at 5 and 10 months of age, respectively. In the animals, neurodegenerative processes and how they were influenced by melatonin were examined. Melatonin (10 mg/kg) or vehicle (ethanol at 0.066%) treatments were administrated from the age of 1 to 9 months in the drinking water. Differences in the neurodegenerative markers examined were found between the two strains with a more damaged protein, phosphorylated Tau at Ser392, increased neurofibrillary tangles (NT) and higher α-synuclein expression in SAMP8 versus SAMR1 mice overall, when the mice were 10 months of age. Changes in density of receptors and oxidative stress-related signaling with age were found in the brains of SAM strains at 10 months as shown by a marked decrease in the level of MT-1 melatonin receptor and retinoic acid receptor-related orphan receptor (ROR)-α1. This diminution was earlier and more pronounced in SAMP8 mice. Likewise, the levels of nuclear factor-kappa B (NF-kB) transcriptional factor were higher in SAMP8 mice compared with SAMR1 mice regardless of age confirming the direct role of oxidative stress in the aging process. Treatment with melatonin in SAMP8 and SAMR1 mice reduced the neurodegenerative changes with an increase of ROR-α1 levels without an apparent influence in the levels of MT-1 receptor. However, different melatonin effects on NF-kB signaling were observed suggesting that NF-kB could trigger inflammatory processes in a different way, being SAM strain-dependent and associated with age-related oxidative stress levels. The effectiveness of melatonin in improving age-related neural impairments is corroborated.
Experimental Gerontology, 2008
We investigated whether chronic melatonin administration influences mitochondrial oxidative stress and life span in mice. Diaphragmatic mitochondria from female senescent prone (SAMP8) and senescent resistant (SAMR1) mice at 5 and 10 months of age were studied. Mitochondrial oxidative stress was determined by measuring the levels of lipid peroxidation, glutathione and glutathione disulfide, and glutathione peroxidase and reductase activities. Mitochondrial function was assessed by measuring the activity of the respiratory chain complexes and the ATP content. The results suggest that the age-dependent mitochondrial oxidative damage in the diaphragm of SAMP8 mice was accompanied by a reduction in the electron transport chain complex activities and in ATP levels. Furthermore, melatonin administration between 1 and 10 months of age normalized the redox and the bioenergetic status of the mitochondria and increased the ATP levels. Melatonin also increased both half-life and longevity, mainly in SAMP8 group. These results suggest an agerelated increase in mitochondria vulnerability to oxidation in SAM mice at 10 months of age that was counteracted by melatonin therapy. The effects of melatonin on mitochondrial physiology probably underline the ability of the indoleamine to increase maximal life span in these animals.