Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA261

Poster Communications

Age-related changes in the oxidative stress, apoptosis, sirtuin 2 and FoxO3a expression in the hippocampus: protective effects of melatonin

A. Keskin-Aktan1,2, S. Abgarmi3, K. G. Akbulut1, H. Akbulut3

1. Physiology, Gazi University, Ankara, Turkey. 2. Physiology, Nuh Naci Yazgan University Health Sciences Faculty, Kayseri, Turkey. 3. Internal Medicine, Ankara University School of Medicine, Ankara, Turkey.

Aging is closely associated with oxidative stress and apoptosis1. Melatonin as a free radical scavenger has anti-apoptotic and anti-aging properties2. The pharmacological inhibitors of sirt2 appear to be neuroprotective in the brain3. We aimed to demonstrate the effects of melatonin administration on age-related changes in the oxidative stress, apoptosis, sirtuin 2 (SIRT2) and FoxO3a expression in the hippocampus. Twenty four Wistar albino male rats (young: 3 months old, aged: 22 months old) were divided into following groups: (1) Young-control, (2) Young-melatonin, (3) Aged-control, (4) Aged-melatonin. Subcutaneous injections of control (1% ethanol-PBS) and melatonin (10 mg/kg/day) groups were maintained for 21 days. SIRT2, FoxO3a, Bcl-2 and Bax expressions were tested by Western blotting. SIRT2 and FoxO3a protein levels were measured by a sandwich ELISA method. Total oxidant status (TOS) and total antioxidant status (TAS) were measured using commercially available kits. The ratio of TOS to TAS, i.e. the oxidative stress index (OSI), was also calculated. ANOVA, Pearson's r were used for statistical analysis (p<0.05). Aging increased TOS, OSI, SIRT2, FoxO3a and pro-apoptotic Bax, and decreased TAS, anti-apoptotic Bcl-2 and Bcl-2/Bax ratio in the hippocampus, whereas melatonin administration in aged rats entirely reversed this pattern (p<0.05). ELISA and Western blot findings were similar for SIRT2 and FoxO3a (p<0.05). Additionally, OSI was positively correlated with SIRT2, FoxO3a, Bax, and negatively correlated with Bcl-2 and Bcl-2/Bax ratio (p <0.05). In aging, melatonin administration may prevent oxidative stress and neuronal loss in the hippocampus. Sirt2 and FoxO3a inhibition may be involved in the neuroprotective effects of melatonin.

Where applicable, experiments conform with Society ethical requirements