title: Glutamine synthetase plays a role in D-galactose-induced astrocyte aging in vitro and in vivo.
abstract: Astrocytes play multiple roles in physiological and pathological conditions in brain. However, little is known about the alterations of astrocytes in age-related changes, and few aging models of the astrocytes in vitro have been established. Therefore, in the present study, we used d-galactose (D-Gal) to establish astrocyte aging model to explore the alterations of astrocytes in brain aging. We also used (1)H nuclear magnetic resonance ((1)H NMR) spectra to verify the metabolic changes in the cerebral cortex of mice injected with D-gal. The results showed that D-gal (55mM) treatment for 1 week induced senescence characteristics in cultured cortical astrocytes. Real-time PCR and western blot analysis showed that the levels of glutamine synthetase (GS) mRNA and protein were strikingly decreased in the cultured senescent astrocytes, and the senescent astrocytes showed less resistance to the glutamate-induced gliotoxicity. The impairments of glutamate-glutamine cycle and astrocytes were also found in the cerebral cortex of mice treatment with D-gal (100mg/kg) for 6 weeks, and the level of GS mRNA was also found to be reduced markedly, being consistent with the result obtained from the senescent astrocytes in vitro. These results indicate that astrocyte may be the predominant contributor to the pathogenic mechanisms of D-gal-induced brain aging in mice, and GS might be one of the potential therapeutic targets of the aged brain induced by D-gal.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Gao
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Shi
authors.affiliation: Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ai
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Yueyang
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: jxlu313@163.com.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D015536:Down-Regulation; D005690:Galactose / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D066244:Proton Magnetic Resonance Spectroscopy; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D005973:Glutamine; D005974:Glutamate-Ammonia Ligase; D005690:Galactose
keywords: Aging; Astrocyte; Glutamine synthetase (GS); d-Galactose (D-gal)