Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway

Abstract

Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer’s disease (AD). However, the molecular mechanisms underlying curcumin’s effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer’s disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

The Seed of <i>Zizyphus jujuba</i> var. <i>spinosa</i> Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

“…Thus, the absence of BDNF action might be responsible for AD symptoms, including neuronal dysfunctions. 10,29,30) Previous reports have shown that a direct 31) or indirect 32) increase of BDNF levels reduces ADlike symptoms.…”

The central role of heat shock factor 1 in synaptic fidelity and memory consolidation

“…A combination of adaptogens, Eleutherococcus senticocus, Schisandra chinensis, and Rhodiola rosea, raises HSP levels (Panossian et al 2009) and improves memory and cognitive performance (Aslanyan et al 2010). Curcumin activates HSF1 (Teiten et al 2009) and augments memory function (Zhang et al 2015a). Capsaicin activates calcium channels (TRPV) and thereby activates HSF1 (Bromberg et al 2013) and improves cognitive function while blocking tau phosphorylation and β-amyloid accumulation in a diabetic-dementia animal model (Yang et al 2015).…”

Neurotrophic effects of turmeric on the memory of the mouse using the Morris water maze test

“…[8,10] Accordingly, Nam et al [9] reported that the protective effect of curcumin is mediated by the prevention of oxidative stress leading to apoptosis. Curcumin as an antioxidant primarily protects biomembranes against peroxidative damage, a free-radical-mediated chain reaction, damaging cell membranes.…”

“…[4] Curcumin's preventative and protective roles on learning and memory is related to apoptotic effect, as it impairs the consolidation of memory and reverses cognitive alterations, by inhibiting programmed cell death. [8,10] Accordingly, Nam et al [9] reported that the protective effect of curcumin is mediated by the prevention of oxidative stress leading to apoptosis. Curcumin as an antioxidant primarily protects biomembranes against peroxidative damage, a free-radical-mediated chain reaction, damaging cell membranes.…”

“…Curcumin has also been shown to reduce the levels of amyloid and oxidized proteins and prevents memory deficits, and is thus beneficial to patients with Alzheimer's disease. [10] Moreover, curcumin also has a close interaction with the cholinergic system in memory retention process and improves memory retention process in rats. [11] A study revealed that curcumin improved learning and memory in mice.…”