Abstract
Aging has been attributed to oxidative stress and inflammatory response, in which NF-κB and Nrf2-ARE signaling pathways play significant roles. Senescence accelerated mouse prone 8 (SAMP8) is generally used an animal model for aging studies. Here, we investigated the NF-κB and Nrf2-ARE signaling pathways in SAMP8 brains at different ages and their responses to SS31 peptide treatment. Thirty six SAMP8 mice were separated into aging groups and SS31-treatment groups. The hippocampus from each mouse was dissected for RNA and protein extraction. Cytokines and ROS levels were measured using ELISA and standardised method. Gene expressions of NF-κB, Nrf2 and HO-1 were measured by RT-qPCR. Total protein amount of NF-κB and HO-1, as well as the concentrations of nuclear and cytoplasmic Nrf2 were measured using Western blots. Our data showed that aging could activate both NF-κB and Nrf2-ARE signaling pathways, which could be suppressed and activated by SS31 treatment respectively. Regression analysis revealed that NF-κB gene expression was the most important parameter predicting aging process and SS31 treatment effects in SAMP8. Our findings suggested that SS31 treatment may modulate the inflammatory and oxidative stress status of the aged brains and exert protective effects during brain aging.
Highlights
Aging, associated with cognitive decline, increases the risk of neurodegenerative disorders and leads to irreversible alterations in humans as well as in experimental animals [1, 2]
Characterization of cytokines and intracellular reactive oxygen species (ROS) production inSAMR1, Senescence accelerated mouse prone 8 (SAMP8) and SAMP8 with SS31 treatment mice compared with 10-month-old Senescence-accelerated mouseresistant 1 (SAMR1) mice using enzyme-linked immunosorbent assay (ELISA)(Table 1)
These results suggested that inflammatory response and oxidative stress might play an important role in senescence and SS31 may target the same molecular pathway/s
Summary
Aging, associated with cognitive decline, increases the risk of neurodegenerative disorders and leads to irreversible alterations in humans as well as in experimental animals [1, 2]. In this process, brain exhibits a progressively increased inflammatory status, which is called as “inflamm-aging” [3]. The eukaryotic transcription factor nuclear factorkappa B (NF-κB) is a master regulator in response to many pathological conditions, such as infectious agents and cellular stress [5]. While NF-κB functions as a cellular survival mechanism in acute responses, this transcription factor may cause neuro-inflammation and contribute deleteriously to agerelated disorders [10]
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