Green Tea Extract and Exercise Disrupt Progress of Alzheimer's Disease in Mice
Introduction
Amyloid-β (Aβ) induced mitochondrial dysfunction may play
a role in the onset and progression of Alzheimer's disease (AD). Therefore,
therapeutics targeted to improve mitochondrial function could be beneficial.
Plant-derived flavonoids have shown promise in improving certain AD phenotypes,
but the overall mechanism of action(s) through which flavonoids protect from AD
is still unknown. From a list of 25 natural product, Epigallocatechin-3-gallate
(EGCG) and luteolin were identified as the top two mitochondrial restorative
compounds from the in vitro screen. The compounds were screened for their
ability to restore altered mitochondrial membrane potential (MMP), reactive
oxygen species (ROS) production, or ATP levels in neuroblastoma cells
expressing mutant amyloid-β protein precursor (AβPP).
Increases in inflammation have been linked to Alzheimer’s
disease patients and recent studies have suggested the benefits of dietary
antioxidants in reducing the risk of AD. Researchers decided to investigate the
effects of voluntary exercise and epigallocatechin-3-gallate (EGCG), a green
tea extract, on memory function and Aβ levels in mice known to show plaque
deposits and behavior deficits.
Methodology
The murine model study investigated the effects of 4
months of wheel-running exercise, initiated at 2-months of age, in conjunction
with the effects of the green tea catechin (-)-epigallocatechin-3-gallate
(EGCG) administered orally in the drinking water (50 mg/kg daily) on:
1) Behavioral Measures: learning and memory performance
in the Barnes maze, nest building, open-field, anxiety in the light-dark box.
2) Soluble Amyloid-β (Aβ)-levels in the cortex and
hippocampus in TgCRND8 (Tg) mice.
Results
In the behavioural studies, the first test was to test
memory and cognition. Mice were placed in the center of a specialized maze and
allowed to move around with the aim of finding the right hole, or “goal box.” In
the second test, small “nestlets,” or squares containing materials to create
nests, were placed in the habitats for different groups of mice. A day later,
nests were scored based on shape and the amount of material used. Mice
exhibiting symptoms of the disease had trouble finding their ways in the maze
also their nests that were poorly formed or erratic. This was correlated by researchers
as the true condition where mice with Alzheimer’s symptoms, much like people,
can be apathetic about their habitat, or have forgotten how to ‘nest’ appropriately.
Researchers then administered EGCG in the drinking water
of the mice and gave them access to running or exercise wheels. After
re-administering the maze and nesting tests, they found remarkable improvements
in the cognitive function and retention in the Alzheimer’s affected mice that
were given EGCG and were allowed to exercise.
In the final part of the experiment, an analysis of mouse
brain tissues to determine the effects of EGCG and exercise on Aβ levels in
affected regions of the brain was performed. A decrease in Aβ level was noted.
The authors conclude as “Oral administration of the
extract, as well as voluntary exercise, improved some of the behavioral
manifestations and cognitive impairments of Alzheimer’s.”
Article Citation: Sun, G. Y.; et. al. Beneficial Effects
of Dietary EGCG and Voluntary Exercise on Behavior in an Alzheimer's Disease
Mouse Model. J Alzheimers Dis 2015, 44, 561-572.
