The effect of oral galactose on oxidative stress in the brain of a transgenic mice model of Alzheimer’s disease

Abstract

AbstractBackgroundChanges in the brain energy metabolism and oxidative stress can be found before development of Aβ plaques in Alzheimer’s disease (AD) and galactose showed potential therapeutic effect in Tg2576 mice AD model. We aimed to investigate changes in the hippocampal (HPC) energy status and oxidative stress before and after galactose treatment in this model.MethodAdult male B6; SJL‐Tg(APPSWE)2576Kha transgenic (TG) mice (Tg2576) and wild types (WT) aged 5 (5M) and 10 (10M) months were used. Oral galactose therapy was given to half of WT (WT+G) and half of TG (TG+G) group for 2 months (200mg/kg/day), while another half of each group received water ad libitum. Protein expression of insulin receptor substrate (total and phosphorylated; IRS, pIRS), AMP‐activated protein kinase (AMPK, p‐AMPK) was measured by western blot. Corticosterone levels were measured by ELISA, and spectrophotometry were used to measure the parameters of oxidative stress (MnSOD; TBARS). Data were analyzed by Kruskal‐Wallis and Mann‐Whitney U‐test (p<0.05).ResultThe levels of corticosterone were decreased in 5M TG mice (p = 0.0055; n = 8) and galactose (5M TG+G) increased it to the levels of control. Galactose decreased MnSOD (p = 0.0329;n = 5) in 10M TG mice. The decrement in p/t IRS ratio (p = 0.043; n = 5) was seen only in 10M TG mice, and galactose (10M TG+G) reversed it to the levels of control. Increased AMPAK levels were found in 5M TG+G (p = 6,5e‐04; n = 5) and 5M WT+G (p = 8,6e‐05; n = 5) groups, while pAMPK was increased only in 5M TG (p = 0.013; n = 5), and decreased in 5M TG+G group after galactose treatment (p = 0.034: n = 5).ConclusionGalactose increased the corticosterone and AMPK levels in young TG mice, while in older TG mice oral galactose had the effect on the level of MnSOD and p/t IRS ratio. The potential therapeutic impact of oral galactose in Tg2576 mice seems to be connected to maintaining of oxidative stress and energy balance and depends on the animal age and AD stage at which the treatment was initiated. Supported by HRZZ IP‐2018‐01‐8938 and the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project “Experimental and clinical research of hypoxic‐ischemic damage in perinatal and adult brain”, GA KK01.1.1.01.0007 funded by the European Union)