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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.

journal_name

J Pineal Res

journal_title

Journal of pineal research

authors

Caballero B,Vega-Naredo I,Sierra V,Huidobro-Fernández C,Soria-Valles C,De Gonzalo-Calvo D,Tolivia D,Gutierrez-Cuesta J,Pallas M,Camins A,Rodríguez-Colunga MJ,Coto-Montes A

doi

10.1111/j.1600-079X.2008.00591.x

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

302-11

issue

eissn

0742-3098

issn

1600-079X

pii

JPI591

journal_volume

pub_type

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Favorable effects of a prolonged treatment with melatonin on the level of oxidative damage and neurodegeneration in senescence-accelerated mice.