Substantia nigra from different ages of Rat and iron-challenged SH-SY5Y transcriptome profile

Iron is known to be gradually accumulated at the substantia nigra region of the midbrain as getting old, considered as one of the main risk factors of Parkinson's disease and other neurodegenerative diseases in humans. Heavy metal ions like iron could induce reactive oxygen species, making toxic stress inside the cell, but how the neurons at the substantia nigra are protected from this age-related iron overload has not been fully elucidated. Here, using the rat brains of different ages, we examined the cellular responses of the region of substantia nigra against the age-related iron accumulation. By analyzing the transcriptome of the region we observed the iron deposition, we identified the elevation of stress response genes in the older animals. To determine the genes related to iron response independent of neurodevelopment also elevated as getting old, we challenged a similar amount of irons to the neuroblastoma cell line SH-SY5Y and analyzed their transcriptomic responses. The pathway related to ER stress by protein folding is significantly upregulated among various stress responses altered by iron overload both at the rat brain and the cell. Our result provides a detailed cellular response of neuronal cells against the iron overload causing age-related neurodegenerative diseases. Overall design : Total RNA was extracted from Substantia nigra in each lobe of 4 male 15-month-old, 4 male 6-month-old, 5 female 6-month-old, and 5 female 6-week-old rat. SH-SY5Y was treated with media mixed with 1mM or 2mM ferrous iron for 4 passages with non-treated control. Triplicate samples were prepared in each concentration.