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Cistanche is very good for Alzheimer's disease

Using a transgenic mouse model of Alzheimer's disease, the scientists demonstrated a clear link between mitochondrial oxidative damage and cognitive dysfunction.

Shibaura Institute of Technology news on February 14

Increased oxidative damage is associated with neurodegenerative diseases such as Alzheimer's disease (AD). Although the pathophysiology of AD has been extensively studied, the possible relationship between mitochondrial dysfunction and the disease remains largely unknown. A research team led by Prof. Koji Fukui from Shibaura Institute of Technology in Japan confirmed that AD progression is associated with oxidative brain damage, which impairs cognitive function in AD transgenic mice in an age-dependent manner.

The mitochondrial electron transport chain required to generate energy in cellular processes also produces reactive oxygen species (ROS), which attack tissues and cause oxidative damage. This damage can lead to mitochondrial dysfunction and even cell death. Since our brain uses more oxygen than other organs, it is more vulnerable to this ROS damage.

According to literature reports, ROS can also lead to the accumulation of β-amyloid (Aβ), which marks the onset of Alzheimer's disease (AD), a severe and irreversible neurodegenerative disease. Current treatments for Alzheimer's disease do not stop its progression, so new treatments need to be developed.

In a previous study, a team of scientists found that older rats deficient in vitamin E had significantly higher levels of oxidation than younger rats. Furthermore, ROS generated by mitochondrial oxidation may damage brain cells, suggesting a strong link between AD and mitochondrial dysfunction. To improve this understanding, the same group of scientists have now shown that AD progression is closely related to oxidative brain damage. The research, led by Prof. Koji Fukui and his colleagues Naoki Yoshida, Yugo Kato and Prof. Hirokatsu Takatsu, was recently published in the journal Biomedicines. "We found that oxidation negatively affects mitochondria, which can lead to cognitive dysfunction," explains Professor Fukui, corresponding author of the study.

The study was published in the journal Biomedicines (latest impact factor: 6.081) on January 26, 2022

The scientists used three groups of AD mice aged 3 months, 6 months and 20 months, as well as healthy controls. To test their cognition and coordination, the researchers performed two well-known experiments on the mice: the Morris water maze and the Rota-rod test. They found that AD mice took longer to complete their maze goals, but did not slow down. In the Rota-rod test, 6- and 20-month-old AD mice stayed on the rod longer, while age-matched control mice descended faster. "The difference in time to fall may be due to the difference in body weight between the two groups of mice, as control mice were heavier than AD mice," explained Prof. Fukui. These results suggest that AD mice have impaired cognitive function, but without any coordination question.

To determine which AD-related proteins were responsible for this cognitive impairment, the authors collected tissue samples from different parts of the brains of the two groups of mice and assessed the levels of oxidative markers in the samples. First, they found that AD mice had higher levels of Aβ, which gradually increased with age. To their surprise, the AD-related protein Aβ1-42 was found in significantly higher levels in the hippocampus than in other parts of the brain. However, they did not find any changes in the levels of tau protein, another marker that accumulates in AD pathology. The results showed that the aggregation of Aβ1-42 in the hippocampus could cause cognitive dysfunction in AD mice.

The team also speculates that ROS-induced mitochondrial damage is closely related to neuronal survival. To test their hypothesis, they measured levels of some key mitochondrial oxidases, including nicotinamide-nucleotide adenosyltransferase (NMNAT)-3, which has anti-aging effects. While NMNAT-3 was found to be decreased, levels of 3-NT (3-nitrotyrosine), a higher indicator of oxidation, increased with age in AD mice. "As NMNAT-3 levels decreased and 3-NT levels increased, it became clear that oxidation leads to mitochondrial dysfunction and, ultimately, cognitive dysfunction," commented Professor Fukui.

The research team is optimistic about the potential impact of the findings, particularly in terms of increasing intake of antioxidant compounds that help our bodies mitigate ROS. In fact, many natural antioxidants, such as vitamin E and vitamin C, can be obtained from the diet. Prof. Fukui speculates and concludes: "If mitochondria can be protected from ROS, mitochondrial function and cognitive function may be maintained. Future research should focus on developing diagnostic markers to detect early changes in the brain, as well as exploring Compounds with high antioxidant activity in mitochondria."