Surgery-induced cognitive dysfunction is alleviated through triggering receptor expressed on myeloid cells 2.

Neuroinflammation plays a key role in perioperative neurocognitive disorders (PND). Increased evidences indicate that triggering receptor expressed on myeloid cells 2 (TREM2) can mitigate inflammatory response in the brain, and the aim of this study is to investigate whether TREM2 is involved in surgery-induced cognitive dysfunction in adult mice. We used adult C57BL/6 mice subjected to intramedullary fixation surgery, and found that surgery did not impair the motor ability of mice, but worsened the learning and memory function, and reduced the expression of TREM2. Meanwhile, up-regulated TREM2 expression in the brain of mice, induced by selective TREM2 agonist HSP60, significantly improved the learning and memory, alleviated the neuroinflammation, and decreased the neuronal cell apoptosis in mice. Meanwhile, TREM2-siRNA abolished the increased expression of TREM2 induced by HSP60, and reversed all the HSP60-induced beneficial effects. Therefore, our study indicated that up-regulation of TREM2 alleviated neuroinflammation and improved learning and memory function after surgery in mice.

Theanine attenuates hippocampus damage of rat cerebral ischemia-reperfusion injury by inhibiting HO-1 expression and activating ERK1/2 pathway.

AIMS: Theanine, as a naturally occurring component in tea, has been shown to deliver benefits against various diseases. However, the exact molecular mechanisms underlying theanine's protective actions against cerebral ischemia/reperfusion (IR) injury still remains largely unknown. MAIN METHODS: In this study, rat cerebral IR injury model was established and were randomly divided into the following five groups: Sham (SH), IR, IR + Theanine (TH), IR + TH+ heme oxygenase-1 (HO-1) inducer cobalt protoporphyrin (Copp), and IR + Copp groups. KEY FINDINGS: We found that theanine significantly inhibited neuron damage and apoptosis in the hippocampus during the 48 h detection period, as detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Meanwhile, reduced levels of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX) were observed in the theanine-treated group. Enzyme-linked immunosorbent (ELISA) assay also revealed that theanine markedly decreased the levels of inflammatory cytokines, such as IL-6, IL-1ß, and TNF-α, in IR rats. The anti-apoptotic effect of theanine on IR injury was further verified by flow cytometry assay. Besides, theanine dramatically inhibited HO-1 expression and activity but increased extracellular signal-regulated kinase 1/2 (ERK1/2) activity in hippocampal tissue from rats with cerebral IR injury. However, co-treatment with Copp remarkably abolished the protective effects of theanine on cerebral IR injury. SIGNIFICANCE: These findings demonstrated that the neuroprotective role of theanine was associated with its anti-oxidative, anti-inflammatory, and anti-apoptotic properties, which might be through regulation of HO-1 activation in rats with cerebral IR injury.