Elsevier

Neuroscience

Volume 169, Issue 3, 1 September 2010, Pages 1296-1306
Neuroscience

Neurodegeneration, Neuroprotection, and Disease-Oriented Neuroscience
Research Paper
Curcuminoids enhance memory in an amyloid-infused rat model of Alzheimer's disease

https://doi.org/10.1016/j.neuroscience.2010.05.078Get rights and content

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease. There are a limited number of therapeutic options available for the treatment of AD. Curcuminoids (a mixture of bisdemethoxycurcumin, demethoxycurcumin and curcumin) is the main chemical constituent found in turmeric, a well known curry spice, having potential in the treatment of AD. The objective of this study was to investigate the effects of curcuminoid mixture and individual constituents on spatial learning and memory in an amyloid-beta (Aβ) peptide-infused rat model of AD and on the expression of PSD-95, synaptophysin and camkIV. Curcuminoid mixture showed a memory-enhancing effect in rats displaying AD-like neuronal loss only at 30 mg/kg, whereas individual components were effective at 3–30 mg/kg. A shorter duration treatment with test compounds showed that the curcuminoid mixture and bisdemethoxycurcumin increased PSD-95 expression in the hippocampus at 3–30 mg/kg, with maximum effect at a lower dose (3 mg/kg) with respective values of 470.5 and 587.9%. However, after a longer duration treatment, two other compounds (demethoxycurcumin and curcumin) also increased PSD-95 to 331.7 and 226.2% respectively at 30 mg/kg. When studied for their effect on synaptophysin in the hippocampus after the longer duration treatment, the curcuminoid mixture and all three individual constituents increased synaptophysin expression. Of these, demethoxycurcumin was the most effective showing a 350.1% increase (P<0.01) at 30 mg/kg compared to the neurotoxin group. When studied for their effect on camkIV expression after longer treatment in the hippocampus, only demethoxycurcumin at 30 mg/kg increased levels to 421.2%. These compounds salvaged PSD-95, synaptophysin and camkIV expression levels in the hippocampus in the rat AD model, which suggests multiple target sites with the potential of curcuminoids in spatial memory enhancing and disease modifying in AD.

Section snippets

Drugs and chemicals

Amyloid beta peptide (1–40) and ibotenic acids were purchased from the Sigma Chemical Company, St. Louis, MO, USA. Curcuminoids (greater than 95% purity; having bisdemethoxycurcumin 4.15%, demethoxycurcumin 16.53% and curcumin 79.52%) and its individual components, bisdemethoxycurcumin (78% purity), demethoxycurcumin (98% purity) and curcumin (98.35% purity) were generous gifts from the Sabinsa Group of Companies, 70 Ethel Road West, Unit 6, Piscataway, NJ 08854, USA. The purity of the

Ink injection into the hippocampus

In order to ensure that the injection procedure adopted in this study was accurate, blue ink was injected first. After completion of the injection procedure, the animal was sacrificed, the brain was isolated and sections were cut to locate blue ink, and presence of which in the hippocampal area (Fig. 3) confirmed that the injection procedure had been precise.

Effect of curcuminoids on memory in the Aβ-infused rat model of AD

To study the ameliorative effect of test compounds on spatial memory in the Aβ-infused rat model of AD, the vehicle was injected daily

Discussion

As memory loss is the main clinical symptom in AD, we studied the effect of curcuminoids using the Morris water maze test, which shows hippocampus-dependent learning and memory. Neurotoxin injection into the bilateral hippocampus resulted in memory loss in rats showing AD-like features. Treatment with curcuminoid mixture at low dose had no memory-enhancing effect evident at any time point, when compared to the neurotoxin group. However, the same dose (3 mg/kg) of the individual compounds showed

Conclusion

To summarize, in this study, individual compounds of the curcuminoids showed a better effect on memory compared to the parent curcuminoid mixture. Furthermore, we demonstrated that curcuminoid mixture, as well as individual components, showed a beneficial effect on the expression levels of genes involved in synaptic plasticity, although the effect varied with time and dose but beneficial effect was apparent even after short treatment of 5 days. Most importantly, we show here that, curcuminoids

Acknowledgments

This study was supported by the Aga Khan University Research Council (URC), Pakistan. Curcuminoid mixture and individual compounds (bisdemethoxycurcumin, demethoxycurcumin and curcumin) were generously provided by Dr. Muhammed Majeed, Founder and CEO of Sabinsa Corporation, New Jersey, U.S.A. We thank Dr. Graeme Cane, Head, Center of English Language, for language correction and Professor Arif Siddiqui for providing stereotaxic apparatus which was used for stereotaxic surgeries.

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