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

Lu Zhang; Yu Fang; Yuming Xu; Yajun Lian; Nanchang Xie; Tianwen Wu; Haifeng Zhang; Limin Sun; Ruifang Zhang; Zhenhua Wang

doi:10.1371/journal.pone.0131525

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

PLoS One. 2015 Jun 26;10(6):e0131525. doi: 10.1371/journal.pone.0131525. eCollection 2015.

Authors

Lu Zhang¹, Yu Fang², Yuming Xu¹, Yajun Lian³, Nanchang Xie³, Tianwen Wu³, Haifeng Zhang³, Limin Sun⁴, Ruifang Zhang⁴, Zhenhua Wang⁴

Affiliations

¹ Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, PR China; Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.
² Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, PR China; Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, PR China.
³ Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.
⁴ Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, PR China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy*
Alzheimer Disease / psychology
Amyloid beta-Peptides / toxicity*
Animals
Brain-Derived Neurotrophic Factor / metabolism*
Cognition / drug effects
Curcumin / administration & dosage*
Disease Models, Animal
MAP Kinase Signaling System / drug effects
Male
Maze Learning / drug effects
Memory Disorders / chemically induced
Memory Disorders / prevention & control*
Memory, Short-Term
Neuroprotective Agents / pharmacology*
Peptide Fragments / toxicity*
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects
Spatial Memory / drug effects*

Substances

Amyloid beta-Peptides
Brain-Derived Neurotrophic Factor
Neuroprotective Agents
Peptide Fragments
amyloid beta-protein (1-42)
Curcumin

Grants and funding

This work was supported by Zhengzhou Science & Technology Basic Research Program (No. 340600531794) and by Henan Science & Technology Basic Research Program (No.122300410365). These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.