Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia

Type 2 diabetes mellitus(T2DM)and Alzheimer's disease(AD)share several common pathophysiological features.Rare variants of triggering receptor expressed on myeloid cells 2(TREM2)increase the risk of developing AD,suggesting the involvement of TREM2 and innate immunity in AD development.It is still unknown whether TREM2 is related to cognitive impairment in T2DM.Here,we investigated the effects of the hippocampal overexpression of TREM2 on cognitive in long-term high-fat diet(HFD)-fed mice.Male C57BL/6J mice were maintained on HFD for 50 weeks.TREM2 was overexpressed in the hippocampus 36 weeks after HFD feeding using adeno-associated virus vector(AAV)-mediated gene delivery.The results showed that the HFD feeding induced rapid and persistent weight gain,glucose intolerance and significant impairments in learning and memory.Compared with AAV-con,AAV-TREM2 significantly ameliorated cognitive impairment without altering body weight and glucose homeostasis in HFD mice.The overexpression of TREM2 upregulated the synaptic proteins spinophilin,PSD95 and synaptophysin,suggesting the improvement in synaptic transmission.Dendritic complexity and spine density in the CA1 region were rescued after TREM2 overexpression.Furthermore,TREM2 markedly increased the number of iba-1/Arg-1-positive microglia in the hippocampus,suppressed neuroinflammation and microglial activation.In sum,hippocampal TREM2 plays an important role in improving HFD-induced cognitive dysfunction and promoting microglial polarization towards the M2 anti-inflammatory phenotype.Our study also suggests that TREM2 might be a novel target for the intervention of obesity/diabetes-associated cognitive decline.

Effects of low and high levels of nano-selenium on intestinal microbiota of Chinese tongue sole(Cynoglossus semilaevis)

Nano-selenium(Se)has attracted growing attention due to its high bioavailability,low toxicity and its possible applications in the prevention of oxidative damage in animal tissues.Recent research works have conveyed that the use of nano-seleniumas food additive could have positive effects on the nutrition of aquatic animals.In this study,the intestinal bacterial communities associated with low and high concentrations of nano-selenium in the diet of Chinese tongue sole were characterized,through 16S rRNA V3–V4 sequencing.Samples were derived from fish fed with diet containing different nano-selenium level,0 mg/kg for the control group,1.6 mg/kg for low dose group,and 2.4 mg/kg for high dose group The intestinal microbial community structure showed a low overall diversity,among which the vibro genus occupied the most important position with more than 90%relative abundance in all three group.Significant differences in specie diversity occurred between the nanoselenium treated(both low dose[IL]and high dose[LH])groups and the control group(IC).Acinetobacter,Arthrobacter,and Streptophytes were the top three enriched genera after the treatment with nano-selenium compared to IC.Meantime,the weight gain rate of the LH group was 9%higher than control.The results revealed the effect of nano-selenium on microbial community structure of gut and growth performance of C.semilaevis,Future research exploring the interaction mechanism between micronutrients and the microbial communities would increase our understanding of the fish nutrition.