Dopamine treatment improves symptoms of Alzheimer’s disease, suggests a study by researchers in Japan

A team from the RIKEN Center for Brain Sciences (CBS) in Japan has discovered a new way to fight Alzheimer’s disease.

Using infected mice, Japanese researchers found that treating dopamine could reduce physical symptoms in the brain and improve memory.

Published Wednesday in the scientific journal Science Signaling, the study examines the role of dopamine in stimulating the production of neprilysin, an enzyme that can break down toxic plaques in the brain that are characteristic of Alzheimer’s disease.

If similar results are obtained in human clinical trials, this could lead to a fundamentally new way of treating the disease.

The formation of hard plaques around neurons is one of the first signs of Alzheimer’s disease, which often begins decades before behavioral symptoms such as memory loss are detected.

These plaques are made up of pieces of beta-amyloid peptide that accumulate over time.

In the new study, the RIKEN CBS laboratory focuses on the enzyme neprilysin because previous experiments have shown that a genetic manipulation that produces too much neprilysin in the brain – a process called upregulation – leads to reduced amyloid-beta plaques and improved memory in mice.

Although it is experimentally useful to genetically manipulate mice to produce neprilysin, treating humans with the disease requires a way to achieve this using drugs.

Neprilysin pills or injections are not feasible because it cannot enter the brain from the bloodstream.

So the first step in the new study was a detailed process of screening multiple molecules to find out which ones can naturally regulate neprilysin in the right parts of the brain.

The team’s previous research narrowed the search down to hormones produced by the hypothalamus and found that dopamine to brain cells grown in the lab led to higher levels of neprilysin and lower levels of beta-amyloid a navigation is free.

The team has now started the tests. Using the DREADD system, the researchers inserted small engineered receptors into dopamine-producing neurons in the ventral tegmental area of ​​mice.

By adding an appropriate concept drug to the mice’s diet, the researchers were able to activate just those neurons in the mice’s brains.

Like the lab dishes, the activity led to an increase in neprilysin and a decrease in free beta-amyloid, except in the frontal part of the brain of the mice.

But could the treatment remove the toxic plaques? The researchers answer in the affirmative. They repeated the experiment using a special mouse model of Alzheimer’s disease in which the animals develop beta-amyloid plaques. Eight weeks of continuous treatment resulted in a significant reduction in the number of plaques in the prefrontal cortex of these mice.

The DREADD system is an “unusual” system for the precise manipulation of specific neurons, but it is not very useful for human clinical situations. The final experiments tested the effects of L-DOPA treatment.

L-DOPA is a dopamine precursor molecule often used to treat Parkinson’s disease because it can enter the brain from the blood, where it is then converted to dopamine.

Treating model mice with L-DOPA resulted in an increase in neprilysin and a decrease in beta-amyloid plaques in the front and back of the brain.

Model mice treated with L-DOPA for 3 months also performed better in memory tests than untreated model mice.

Experiments showed that neprilysin levels naturally decreased with age in normal mice, especially in the frontal part of the brain, which could make it a good biomarker for detecting preclinical Alzheimer’s disease or in danger.

It is not yet known how dopamine causes an increase in neprilysin levels and this is the next research topic for the Japanese laboratory.

“We showed that treatment with L-DOPA can help reduce harmful beta-amyloid plaques and improve memory function in a mouse model of Alzheimer’s disease,” explained Watamura Naoto, first author of the study, in a statement from the center.

“But L-DOPA treatment is known to have serious side effects in Parkinson’s patients. Therefore, our next step is to study how dopamine regulates neprilysin in the brain, which should lead to a new protective mechanism that can be initiated in the pre-clinical stage of the disease. Alzheimer’s,” said the Japanese researcher.

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