Curcuminoids enhance memory in an amyloid-infused rat model of Alzheimer's disease.
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 (Abeta) 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.
Natural Products Research Unit, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi-74800, Pakistan.
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T
Ahmed
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Enam
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AH
Gilani
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology*; D016229:Amyloid beta-Peptides; D000818:Animals; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000096:biosynthesis; D002452:Cell Count; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D036381:Diarylheptanoids; D000076122:Disks Large Homolog 4 Protein; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008568:Memory / Q000187:drug effects*; D009473:Neuronal Plasticity; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010446:Peptide Fragments; D051381:Rats; D017207:Rats, Sprague-Dawley; D016708:Synaptophysin / Q000096:biosynthesis; D013997:Time Factors
D016229:Amyloid beta-Peptides; D036381:Diarylheptanoids; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D016708:Synaptophysin; C078592:amyloid beta-protein (1-40); C034786:bisdemethoxycurcumin; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517686:Camk4 protein, rat; D003474:Curcumin; C050229:demethoxycurcumin