Although animal models of depression are produced by loading chronic stress, inducing neuroinflammation, or administering drugs that induce depression, the results obtained in these models have poor ...reproducibility. Therefore, it is necessary to develop animal models that exhibit definitive symptoms of depression for studies on potential therapeutics. This study aimed to investigate depressive symptoms and their pathogenesis in lipopolysaccharide (LPS)-inflamed mice treated with dexamethasone (DEX). Male ICR mice were injected with LPS, followed by injection with DEX at day later once daily for 6 days. Mice in the LPS+DEX group had significantly longer immobility time in the tail-suspension and forced swim tests than did those in the LPS or DEX only and control groups at 7 days post-LPS administration. In immunohistochemical analysis, significantly lower number of the immature neuronal marker doublecortin-positive cells were observed in the hippocampal dentate gyrus of mice in the LPS+DEX group compared with those of mice in the LPS or DEX only and control groups at 7 days after LPS administration. These results suggest that repeated DEX administration to LPS-inflamed mice may induce definitive symptoms of depression by decreasing the number of immature neurons in the hippocampal dentate gyrus.
Ergothioneine (ERGO) is a hydrophilic antioxidant contained in the food and is distributed to the brain after oral intake, exhibiting a neuroprotective effect. ERGO protected PC12 cells against ...cellular toxicity induced by amyloid beta (Aβ) and improved impairment of learning and memory ability in mice administered with Aβ. However, the effects of ERGO on hyperphosphorylation of tau protein is unclear. In the present study, we investigated whether ERGO suppresses Aβ-induced hyperphosphorylation of tau protein in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were differentiated using culture medium containing 1% or 10% fetal bovine serum (FBS) with 10 μM retinoic acid. Exposure to Aβ25-35 clearly decreased cellular viability in SH-SY5Y cells differentiated in the 10% FBS medium, but not 1% FBS medium. Pretreatment with ERGO protected SH-SY5Y cells against cellular toxicity induced by Aβ25-35 in a dose-dependent manner. Exposure of SH-SY5Y cells to Aβ25-35 increased expression of phosphorylated tau protein, and the increase was suppressed by pretreatment with ERGO in a dose-dependent manner. These results suggest that ERGO may suppress hyperphosphorylation of tau protein and alleviate neurotoxicity induced by Aβ.