Retracted: Mechanisms and effects of curcumin on spatial learning and memory improvement in APPswe/PS1dE9 mice

Abstract

Evidence suggests that curcumin, the phytochemical agent in the spice turmeric, might be a potential therapy for Alzheimer's disease (AD). Its antioxidant, anti-inflammatory properties have been investigated extensively. Studies have also shown that curcumin can reduce amyloid pathology in AD. The underlying mechanism, however, is complex and is still being explored. In this study, we used the APPswe/PS1dE9 double transgenic mice, an AD model, to investigate the effects and mechanisms of curcumin in the prevention and treatment of AD. The water maze test indicated that curcumin can improve spatial learning and memory ability in mice. Immunohistochemical staining and Western blot analysis were used to test major proteins in β-amyloid aggregation, β-amyloid production, and β-amyloid clearance. Data showed that, 3 months after administration, curcumin treatment reduced Aβ40 , Aβ42 , and aggregation of Aβ-derived diffusible ligands in the mouse hippocampal CA1 area; reduced the expression of the γ-secretase component presenilin-2; and increased the expression of β-amyloid-degrading enzymes, including insulin-degrading enzymes and neprilysin. This evidence suggests that curcumin, as a potential AD therapeutic method, can reduce β-amyloid pathological aggregation, possibly through mechanisms that prevent its production by inhibiting presenilin-2 and/or by accelerating its clearance by increasing degrading enzymes such as insulin-degrading enzyme and neprilysin.

Effects of curcumin on synapses in APPswe/PS1dE9 mice

“…29 We have previously reported that curcumin improves the spatial learning and memory abilities of APPswe/ PS1dE9 double transgenic mice. 23 Therefore, we sought to determine whether curcumin affects the pathology of AD via the synapses. Specifically, we sought to determine whether curcumin influences the structures and functions of the synapses of APPswe/PS1dE9 double transgenic mice.…”

“…The following doses were used in the curcumin treatment groups: the low-dose curcumin group (LDC) received 100 mg/kg/day, the medium-dose curcumin group (MDC) received 200 mg/kg/day, and the high-dose curcumin group (HDC) received 400 mg/kg/day. 23 …”

Curcumin ameliorates insulin signalling pathway in brain of Alzheimer’s disease transgenic mice

“…Then, we placed the cryovials into liquid nitrogen to freeze them and subsequently stored them at −80°C until the tissues were used for a western blot analysis. 9 …”

“…12 The CA1 region of the hippocampus is the core functional area of learning and memory; therefore, we chose this region of the APPswe/PS1dE9 double transgenic mice as the research object. 13 9 The experiments were strictly performed abiding by the regulations and the guidelines of Beijing for the use of animals in research, and we received permission from the Animal Research Ethics Board of Dongzhimen Hospital. The mice were kept in a temperature-controlled environment with 12 h of light and 12 h of dark.…”

Is the Combination/Multi-target Therapy a New Promise for Alzheimer's Disease?

“…In a 4 weeks randomized, double-blind, placebo-controlled human trial, curcumin (400 mg) has been shown to significantly improve working memory and mood after treatment [35]. In animal studies of curcumin in APPswe/PS1dE9 double transgenic AD mice also showed improved spatial learning and memory ability [36,37]. Such effects may conducted through reducing Aβ40, Aβ42, and aggregation of Aβ-derived diffusible ligands in the mouse hippocampal CA1 area, increase the expression of synapse-related proteins PSD95 and Shank1 and improve structure and plasticity of synapse.…”