title: Fibroblast growth factor 21 protects mouse brain against D-galactose induced aging via suppression of oxidative stress response and advanced glycation end products formation.
abstract: Fibroblast growth factor 21 (FGF21) is a hormone secreted predominantly in the liver, pancreas and adipose tissue. Recently, it has been reported that FGF21-Transgenic mice can extend their lifespan compared with wild type counterparts. Thus, we hypothesize that FGF21 may play some roles in aging of organisms. In this study d-galactose (d-gal)-induced aging mice were used to study the mechanism that FGF21 protects mice from aging. The three-month-old Kunming mice were subcutaneously injected with d-gal (180mg·kg(-1)·d(-1)) for 8weeks and administered simultaneously with FGF21 (1, 2 or 5mg·kg(-1)·d(-1)). Our results showed that administration of FGF21 significantly improved behavioral performance of d-gal-treated mice in water maze task and step-down test, reduced brain cell damage in the hippocampus, and attenuated the d-gal-induced production of MDA, ROS and advanced glycation end products (AGEs). At the same time, FGF21 also markedly renewed the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total anti-oxidation capability (T-AOC), and decreased the enhanced total cholinesterase (TChE) activity in the brain of d-gal-treated mice. The expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and member-anchored receptor for AGEs (RAGE) declined significantly after FGF21 treatment. Furthermore, FGF21 suppressed inflamm-aging by inhibiting IκBα degradation and NF-κB p65 nuclear translocation. The expression levels of pro-inflammatory cytokines, such as TNF-α and IL-6, decreased significantly. In conclusion, these results suggest that FGF21 protects the aging mice brain from d-gal-induced injury by attenuating oxidative stress damage and decreasing AGE formation.
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors: Yinhang
authors: Y
authors: Yu
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors: Fuliang
authors: F
authors: Bai
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Function Gene, Harbin 150030, China.
authors: Wenfei
authors: W
authors: Wang
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors: Yaonan
authors: Y
authors: Liu
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors: Qingyan
authors: Q
authors: Yuan
authors: Institute of Psychology, Chinese Academy of Sciences, 100101, China.
authors: Susu
authors: S
authors: Qu
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors: Tong
authors: T
authors: Zhang
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
authors: Guiyou
authors: G
authors: Tian
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Harbin University of Commerce, Harbin 150028, China.
authors: Siming
authors: S
authors: Li
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Function Gene, Harbin 150030, China. Electronic address: deshanli@163.com.
authors: Deshan
authors: D
authors: Li
authors: Bio-Pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Function Gene, Harbin 150030, China. Electronic address: renguiping@126.com.
authors: Guiping
authors: G
authors: Ren
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D005346:Fibroblast Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D005690:Galactose / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D005690:Galactose
keywords: AGEs; Aging; FGF21; Inflammation; Oxidative stress; d-galactose