title: l-Theanine attenuates cadmium-induced neurotoxicity through the inhibition of oxidative damage and tau hyperphosphorylation.
abstract: Cadmium (Cd) has long been known to induce neurological degenerative disorders. We studied effects of l-theanine, one of the major amino acid components in green tea, on Cd-induced brain injury in mice. Male ICR mice were intraperitoneally injected with l-theanine (100 or 200mg/kg/day) or saline and after one hour these mice were orally administrated with CdCl2(3.75-6mg/kg). The treatment was conducted for 8 weeks. l-Theanine significantly reduced Cd level in the mouse brain and plasma. Cd-induced neuronal cell death in the mouse cortex and hippocampus were apparently inhibited by l-theanine treatment. l-Theanine also decreased the levels of malondialdehyde (MDA) and ROS, and obviously elevated the levels of glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the mouse brain. Hyperphosphorylation of tau protein is proposed to be an early event for the evolution of tau pathology, and may play an important role in Cd-induced neurodegeneration. Our results showed that l-theanine significantly suppressed Cd-induced tau protein hyperphosphorylation at Ser199, Ser202, and Ser396. Mechanism study showed that l-theanine inhibited the activation of glycogen synthase kinase-3β (GSK-3β) which contributed to the hyperphosphorylation of tau and Cd-induced cytotoxicity. Furthermore, l-theanine reduced Cd-induced cytotoxicity possibly by interfering with the Akt/mTOR signaling pathway. In conclusion, our study indicated that l-theanine protected mice against Cd-induced neurotoxicity through reducing brain Cd level and relieved oxidative damage and tau hyperphosphorylation. Our foundings provide a novel insight into the potential use of l-theanine as prophylactic and therapeutic agents for Cd-induced neurodegenerative diseases.
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China; Department of Biochemistry, Chuzhou City Vocation College, Chuzhou, Anhui, PR China.
authors.forename: Peiling
authors.initials: P
authors.lastname: Ben
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Aiying
authors.initials: A
authors.lastname: Xiong
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Shidao Community Health Service Center, Rongcheng, Shandong, PR China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Mu
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China. Electronic address: yinzhimin@njnu.edu.cn.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China. Electronic address: lanluo@nju.edu.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000139:chemically induced* / Q000188:drug therapy*; D002104:Cadmium / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005971:Glutamates / Q000627:therapeutic use*; D005978:Glutathione; D005979:Glutathione Peroxidase / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D005971:Glutamates; D016875:tau Proteins; D002104:Cadmium; D008315:Malondialdehyde; C026166:theanine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: Cadmium; Neurotoxicity; Oxidative stress; Tau hyperphosphorylation; l-Theanine