title: Favorable effects of a prolonged treatment with melatonin on the level of oxidative damage and neurodegeneration in senescence-accelerated mice.
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 alpha-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)-alpha1. 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-alpha1 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.
authors.affiliation: Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Caballero
authors.forename: Ignacio
authors.initials: I
authors.lastname: Vega-Naredo
authors.forename: Verónica
authors.initials: V
authors.lastname: Sierra
authors.forename: Covadonga
authors.initials: C
authors.lastname: Huidobro-Fernández
authors.forename: Clara
authors.initials: C
authors.lastname: Soria-Valles
authors.forename: David
authors.initials: D
authors.lastname: De Gonzalo-Calvo
authors.forename: Delio
authors.initials: D
authors.lastname: Tolivia
authors.forename: Javier
authors.initials: J
authors.lastname: Gutierrez-Cuesta
authors.forename: Merce
authors.initials: M
authors.lastname: Pallas
authors.forename: Antonio
authors.initials: A
authors.lastname: Camins
authors.forename: María Josefa
authors.initials: MJ
authors.lastname: Rodríguez-Colunga
authors.forename: Ana
authors.initials: A
authors.lastname: Coto-Montes
mesh_terms: D000375:Aging / Q000187:drug effects*; D019588:Aging, Premature / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016631:Lewy Bodies; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000187:drug effects; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D052002:NF-kappa B p50 Subunit; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D044122:Receptor, Melatonin, MT1; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D051844:alpha-Synuclein; D016875:tau Proteins; C073701:Nfkb1 protein, mouse; D008550:Melatonin