Several neurodegenerative conditions including Alzheimer's and Parkinson's diseases appear in the later stages of life due to loss of specific neuronal populations, protein aggregation with formation of intracellular inclusion bodies, elevated oxidative stress as well as alterations in calcium homeostasis and cytoskeletal destabilization. The concentration of radical oxygen species (ROS) and consequently oxidative damage in DNA, proteins and lipids, has been increased with age, playing a key role in neurodegenerative diseases and aging. A valuable animal model to study the mechanisms related to the processes of aging and neurodegenerative diseases is the SAM strain (Senescence-accelerated mice) and SAMP8 mouse, with its neuropathological deficits in learning and memory, appears to be an excellent model to examine the physiopathology of early defects seen in Alzheimer's disease and several age-related pathological alterations. Moreover, Melatonin, the main secretory product of the pineal gland, also functions in the defence of cells from a variety of free-radical related processes and its ability to prevent degenerative diseases in which radical generation is involved is well documented.

Aim: 

Study of oxidative stress effect on the neurodegeneration and the beneficial role of melatonin in this process using SAM mice as animal model

Methods: 

We have been worked with SAMP8 and senescence-accelerated resistant mice (SAMR1) at 5 and 10 months of age studying the role of oxidative stress in their alterations and how melatonin could be able to reduce this damage.

Results: 

Under the cited conditions we have observed changes in density of receptors and oxidative stress-related signaling with age in the brains of SAM strains at 10 months. Treatment with melatonin in SAMP8 and SAMR1 mice reduced the neurodegenerative changes with an increase of retinoic acid receptor-related orphan receptor (ROR-a1) levels without an apparent influence in the levels of MT-1 melatonin receptor. However, different melatonin effects on NF-kB signaling were observed.

Conclusion: 

The effectiveness of melatonin in improving age-related neural impairments was newly corroborated in our studies. Likewise, NF-kB could trigger inflammatory processes in a different way, being SAM strain-dependent and associated with age-related oxidative stress levels.