Melatonin plus physical exercise are highly neuroprotective in the 3xTg-AD mouse.
Study Goal
The researchers aimed to determine the neuroprotective effects of melatonin, alone and combined with physical exercise, in a mouse model of Alzheimer's disease.
Results Summary
Melatonin decreased hyperphosphorylated tau and immunosenescence, protected against cognitive impairment, brain oxidative stress, and mitochondrial DNA loss, and showed additive effects when combined with physical exercise.
Population
3xTg-AD male mice aged 6 to 12 months (moderate to advanced Alzheimer's pathology).
Effective Dosage
Not specified
Duration
6 months
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
physical exercise | decrease | soluble amyloid β oligomers | 3xTg-AD male mice aged from 6 to 12 months | - | decreased | #1 |
melatonin | decrease | soluble amyloid β oligomers | 3xTg-AD male mice aged from 6 to 12 months | - | decreased | #2 |
melatonin | decrease | hyperphosphorylated tau | 3xTg-AD male mice aged from 6 to 12 months | - | decreased | #3 |
melatonin | decrease | immunosenescence | 3xTg-AD mice | - | effective against | #4 |
voluntary physical exercise | decrease | behavioral and psychological symptoms of dementia such as anxiety, a lack of exploration, and emotionality | 3xTg-AD male mice aged from 6 to 12 months | - | protected against | #5 |
physical exercise | decrease | cognitive impairment | 3xTg-AD male mice aged from 6 to 12 months | - | protected against | #6 |
melatonin | decrease | cognitive impairment | 3xTg-AD male mice aged from 6 to 12 months | - | protected against | #7 |
physical exercise | decrease | brain oxidative stress | 3xTg-AD male mice aged from 6 to 12 months | - | protected against | #8 |
melatonin | decrease | brain oxidative stress | 3xTg-AD male mice aged from 6 to 12 months | - | protected against | #9 |
physical exercise | decrease | decrease in mitochondrial DNA (mtDNA) | 3xTg-AD male mice aged from 6 to 12 months | - | protected against | #10 |
melatonin | decrease | decrease in mitochondrial DNA (mtDNA) | 3xTg-AD male mice aged from 6 to 12 months | - | protected against | #11 |
physical exercise plus melatonin | decrease | decrease of mitochondrial complexes | 3xTg-AD male mice aged from 6 to 12 months | - | effective against | #12 |
Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. Several healthy lifestyle options and over-the-counter drugs that it has been suggested delay the onset of the disease are in an experimental phase, but it is unclear whether they will have any therapeutic value against AD. We assayed physical exercise and melatonin in 3xTg-AD male mice aged from 6 to 12 months, therefore from moderate to advanced phases of AD pathology. Analysis of behavior and brain tissue at termination showed differential patterns of neuroprotection for the 2 treatments. Both treatments decreased soluble amyloid β oligomers, whereas only melatonin decreased hyperphosphorylated tau. Melatonin was effective against the immunosenescence that 3xTg-AD mice present. Voluntary physical exercise protected against behavioral and psychological symptoms of dementia such as anxiety, a lack of exploration, and emotionality. Both treatments protected against cognitive impairment, brain oxidative stress, and a decrease in mitochondrial DNA (mtDNA). Interestingly, only the combined treatment of physical exercise plus melatonin was effective against the decrease of mitochondrial complexes. Therefore, melatonin plus physical exercise may exert complementary, additive, or even synergistic effects against a range of disturbances present in AD.