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Context: Neuroligin-1 (NLGN1) is a cell adhesion protein located on the excitatory postsynaptic membrane. β-Amyloid (Aβ)-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 μg/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 ± 0.1482/1.2554 ± 0.3570 vs. 1.6578 ± 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 ± 0.1611/0.8241 ± 0.0964 vs. 0.5587 ± 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.

Although the exact cause of Alzheimer's disease (AD) remains elusive, mounting evidence continues to support the involvement of neuroinflammation in the development of AD. Triptolide isolated from the herb Tripterygium wilfordii Hook F has anti-inflammatory and immunosuppressive activities. In this study, we observed the effects of triptolide on dendritic spines of hippocampal neurons in model rats with AD. Thirty male SD rats were randomly divided into control group, AD model group and triptolide-treated group. The AD model group was made with bilateral microinjection of aggregated beta-amyloid protein (Aβ)1-40 into hippocampus in rats and the control group rats were injected with normal saline in the same way. The triptolide-treated group rats were administered triptolide intraperitoneally for 30 days after microinjection of aggregated Aβ1-40 into hippocampus. Dendritic morphology of hippocampal neurons in each group was analyzed using Golgi staining and ImageJ software. Our data showed that the total number of intersection points of dendrites and spine density in hippocampal neurons in the AD model group were decreased as compared with the control group. However, the total number of intersection points of dendrites and spine density in hippocampal neurons in the triptolide-treated group were increased as compared with the AD model group. Our results indicate that triptolide can alleviate the degeneration of dendritic spines in hippocampal neurons in model rats with AD.

Due to the immunoinflammatory pathology of Alzheimer's disease (AD) brain, recent studies have begun to focus attention on the role of anti-inflammatory drugs or immunomodulators in AD. Triptolide isolated from the herb Tripterygium wilfordii Hook F has anti-inflammatory and immunosuppressive activities. In this study, we observed the effects of triptolide on synaptophysin expression in AD cellular model. AD cellular model was established by action of Aβ-stimulated microglial conditioned medium (MCM) on cultured rat hippocampal neurons (HN). Immunocytochemical staining, western blot and RT-PCR were used to observe the effects of triptolide at different dosages on the synaptophysin expression of hippocampal neurons in AD cellular model at different time points during incubation of cultures. After 24 h of cultivation, the expression level of synaptophysin in MCM/HN model group was decreased as compared with normal HN group and MCM/HN control group, and the expression level of synaptophysin in MCM/HN low-dose triptolide group and MCM/HN high-dose triptolide group was increased as compared with MCM/HN model group. It is concluded that triptolide can promote the synaptophysin expression of hippocampal neurons in the AD cellular model., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Although the exact cause of Alzheimer's disease (AD) remains elusive, mounting evidence continues to support the involvement of neuroinflammation in the development of AD. Triptolide isolated from the herb Tripterygium wilfordii Hook F has anti-inflammatory and immunosuppressive activities. In this study, we observed the effects of triptolide on dendritic spines of hippocampal neurons in model rats with AD. Thirty male SD rats were randomly divided into control group, AD model group and triptolide-treated group. The AD model group was made with bilateral microinjection of aggregated beta-amyloid protein (Aβ) into hippocampus in rats and the control group rats were injected with normal saline in the same way. The triptolide-treated group rats were administered triptolide intraperitoneally for 30 days after microinjection of aggregated Aβ into hippocampus. Dendritic morphology of hippocampal neurons in each group was analyzed using Golgi staining and ImageJ software. Our data showed that the total number of intersection points of dendrites and spine density in hippocampal neurons in the AD model group were decreased as compared with the control group. However, the total number of intersection points of dendrites and spine density in hippocampal neurons in the triptolide-treated group were increased as compared with the AD model group. Our results indicate that triptolide can alleviate the degeneration of dendritic spines in hippocampal neurons in model rats with AD. [ABSTRACT FROM AUTHOR]