L-Theanine attenuates cadmium-induced neurotoxicity through the inhibition of oxidative damage and tau hyperphosphorylation

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 200 mg/kg/day) or saline and after one hour these mice were orally administrated with CdCl2 (3.75-6 mg/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-3 beta (GSK-3 beta 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 theanine as prophylactic and therapeutic agents for Cd-induced neurodegenerative diseases. (C) 2016 Elsevier B.V. All rights reserved.