Curcuminoids enhance memory in an amyloid-infused rat model of Alzheimer's disease.
Alzheimer’s disease (AD) is one of the most common forms of dementia, accounting for 50–60% of dementia cases. Generally brain of AD patients is found to be deposited with extracellular amyloid plaques and intracellular neurofibrillary tangles.
Various compounds derived from the medicinal plants, including turmeric have been known to play a significant role in many diseases, particularly in dementia and Curcumin is the main chemical constituent that imparts such valuable effects. Although Curcuminoid, a key constituent of turmeric, is a mixture of three chemical constituents (Bisdemethoxycurcumin 3–5%, Demethoxycurcumin 15–20% and Curcumin 75–80%), several studies have used Curcumin and Curcuminoid as the same entity probably because Curcumin constitutes the major part, and it is the most extensively studied constituent.
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.
- Male, Sprague–Dawley rats (180–250 g and 14–18 weeks of age) were injected either with 2 µL of neurotoxin (mixture of 1 µL amyloid solution plus 1 µL ibotenic acid solution) or saline into the hippocampus
- After surgery, the animals were allowed to recover for a day in their cages
- Compounds treatment was started on post-operative day 2
- Effect of compounds was tested for a short duration (i.e. 5 days treatment) and a long duration (i.e. 20 days treatment)
- Expression of various genes after drug treatment was studied using a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) method with slight modifications
- Animals were subjected for Morris water maze test to evaluate ameliorative effects of the compounds
- At the end of the trial, rats were sacrificed and the hippocampus and frontal cortex were isolated for RNA extraction and further gene expression studies
Results and Discussion:
- Long duration study results demonstrated that both curcuminoid mixture and all three individual components at 30 mg/kg dose showed a significant effect (p<0.05) at a time point (day 6) compared to the neurotoxin group
- Expression of PSD-95 was increased by curcuminoid mixture and Bisdemethoxycurcumin, in shorter duration treatment, at 3–30 mg/kg, with maximum effect at a lower dose (3 mg/kg)
- Whereas, longer duration treatment revealed that at 30 mg/kg, Demethoxycurcumin and Curcumin increased PSD-95 expression
- Increased expression of synaptophysin was seen when treated with curcuminoid mixture and all three individual constituents
- However, only demethoxycurcumin at 30 mg/kg increased camkIV expression when tested after longer treatment in the hippocampus
Overall, these findings suggested that at varied time and dose curcuminoid mixture, as well as individual components, showed a beneficial effect on the expression levels of genes involved in synaptic plasticity. Thus, suggesting that potential effects of Curcuminoids involves multiple target sites in spatial memory enhancing and disease modifying in AD.