Triggering receptor expressed in myeloid cells (TREM)2 is a genetic high‐risk factor for sporadic Alzheimer's disease (AD) and is considered a potential target for AD diagnosis and therapy, although its role in the different stages of AD remains controversial. We generated an embryonic deletion of Trem2 (whole body deletion) and induced hippocampa1‐ and cortical‐specific knockdown of microglial Trem2 at different stages of the AD process in amyloid precursor protein/Psen1 mice by adeno‐associated virus (AAV) infection. AAV infection induced microglial Trem2 overexpression in the hippocampus of wild‐type (WT) and thymus cell antigen 1–enhanced green fluorescent protein mice. Mice were subjected to ethological and pathologic tests. Whole body genetic deletion of Trem2 exerted different electrophysiological outcomes between different AD pathologic stages, which results from a complex integration of synaptic loss and amyloid aggregation. Interestingly, knockdown of Trem2 at the early‐middle stage of AD (2–6 mo) prevents synaptic loss through directly inhibiting microglial phagocytosis, whereas knockdown of Trem2 at the middle‐late stage of AD (6–10 mo) accelerates synaptic dysfunction because of more severe amyloid deposition caused by the depression of microglial phagocytosis. Additionally, hippocampal overexpression of Trem2 in WT mice results in significant synaptic impairment. Here, with transgenic technology and electrophysiological assay, we revealed that TREM2 up‐regulation promotes microglial phagocytosis equally against synapse and amyloid plaques and eventually results in different outcomes. During the early‐middle pathologic stage, TREM2 enhancing microglial phagocytosis mainly causes synaptic loss. However, TREM2 up‐regulating microglial phagocytosis gradually supports a positive role when amyloid deposition occupies the leading position at the middle‐late pathologic stage. In this study, we highlighted that TREM2 triggers synaptic loss during AD pathology development.—Sheng, L., Chen, M., Cai, K., Song, Y., Yu, D., Zhang, H., Xu, G. Microglial Trem2 induces synaptic impairment at early stage and prevents amyloidosis at late stage in APP/PS1 mice. FASEB J. 33,10425‐10442 (2019). http://www.fasebj.org

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IntroductionTo examine the effects of tap dance (TD) on dynamic plantar pressure, static postural stability, ankle range of motion (ROM), and lower extremity functional strength in patients at risk of diabetic foot (DF).Research design and methodsA randomised, single-blinded, two-arm prospective study of 40 patients at risk of DF was conducted. The intervention group (n=20) received 16 weeks of TD training (60 min/session×3 sessions/week). The control group attended four educational workshops (1 hour/session×1 session/month). Plantar pressure, represented by the primary outcomes of peak pressure (PP) and pressure-time integral (PTI) over 10 areas on each foot, was measured using the Footscan platform system. Secondary outcomes comprised static postural stability, ankle ROM and lower extremity functional strength.ResultsReductions in intervention group PP (right foot: mean differences=4.50~27.1, decrease%=25.6~72.0; left foot: mean differences=−5.90~6.33, decrease%=−22.6~53.2) and PTI at 10 areas of each foot (right foot: mean differences=1.00~12.5, decrease%=10.4~63.6; left foot: mean differences=0.590~25.3, decrease%=21.9~72.6) were observed. Substantial PP and PTI differences were noted at the second through fourth metatarsals, medial heel and lateral heel in the right foot. Substantial PP and PTI differences were detected at metatarsals 1 and 2 and metatarsal 2 in the left foot, respectively. Moderate training effects were found in plantar flexion ROM of both feet, lower extremity functional strength, and length of center-of-pressure trajectory with eyes closed and open (r=0.321–0.376, p<0.05).ConclusionsA 16-week TD training program can significantly improve ankle ROM, lower extremity functional strength, and static postural stability. To attain greater improvements in plantar pressure, a longer training period is necessary.Trial registration numberChiCTR1800014714.

We investigated the effects of chrysin (CHR) on nonalcoholic fatty liver disease (NAFLD) in mice. The NAFLD mouse model was established using a diet deficient in methionine and choline (MCD). CHR was shown to attenuate MCD‐induced hepatic fat accumulation, increase very low‐density lipoprotein (VLDL) secretion, and decrease hepatic oxidative stress in NAFLD mice. Inhibition of oxidative stress or direct suppression of protein kinase C (PKC) by CHR significantly reduced PKC activity in the liver, leading to a decrease in inhibitory phosphorylation of hepatocyte nuclear factor 4α (HNF4α). The resulting activation of HNF4α led to induced transcription of apolipoprotein B and VLDL secretion. Together, these results show that CHR effectively ameliorates MCD‐induced fatty liver in NAFLD mice by targeting the hepatic oxidative stress/PKC/HNF4α signaling pathway.