%0 Journal Article
%T Epigenetic mechanisms underlying the effects of triptolide and tripchlorolide on the expression of neuroligin-1 in the hippocampus of APP/PS1 transgenic mice
%A Baolin Yang
%A Bin Wan
%A Cheng L¨¹
%A Hao Yu
%A Jing Nie
%A Ming Zhang
%A Xiaoling Hu
%A Xiaomei Lu
%J Pharmaceutical Biology
%D 2019
%R https://doi.org/10.1080/13880209.2019.1629463
%X Abstract Context: Neuroligin-1 (NLGN1) is a cell adhesion protein located on the excitatory postsynaptic membrane. ¦Â-Amyloid (A¦Â)-induced neuroinflammation decreases NLGN1 expression through epigenetic mechanisms. Triptolide (T10) and tripchlorolide (T4) exert protective effects on synapses in Alzheimer's disease (AD) mice, but the mechanisms remain unclear. Objective: The effects of T10 and T4 on hippocampal NLGN1 expression in AD mice and the epigenetic mechanisms were assessed using chromatin immunoprecipitation and methylated DNA immunoprecipitation. Materials and methods: Sixty APP/PS1 transgenic mice were randomly divided into an AD model group, a T10-treated group and a T4-treated group (n£¿=£¿20); 20 wild-type littermates served as the control group. APP/PS1 transgenic mice were intraperitoneally injected with T10 (0.1£¿mg/kg) and T4 (25£¿¦Ìg/kg) once per day for 60 days. NLGN1 expression was examined using western blotting and quantitative PCR. Results: T10 and T4 increased the levels of the NLGN1 protein and mRNA in hippocampus of AD mice. T10 and T4 inhibited the binding of HDAC2 (p< 0.01) and MeCP2 (p< 0.01 and p< 0.05, respectively) to the NLGN1 promoter, and cytosine methylation (1.2305£¿¡À£¿0.1482/1.2554£¿¡À£¿0.3570 vs. 1.6578£¿¡À£¿0.1818, p< 0.01) at the NLGN1 promoter in the hippocampus of AD mice. T10 and T4 increased the level of acetylated histone H3 (0.7733£¿¡À£¿0.1611/0.8241£¿¡À£¿0.0964 vs. 0.5587£¿¡À£¿0.0925, p< 0.01) at the NLGN1 promoter in the hippocampus of AD mice. Conclusions: T10 and T4 may increase hippocampal NLGN1 expression in AD mice through epigenetic mechanisms, providing a new explanation for the mechanism underlying the protective effects of T10 and T4 on synapses
%U https://www.tandfonline.com/doi/full/10.1080/13880209.2019.1629463