NMN May Improve Depression

Depression is the fourth largest disease burden globally and one of the leading causes of functional disability in patients. According to the latest data from the World Health Organization, about 1 in 7 people in the world will suffer from depression at some point in their lives. By 2020, depression is expected to become the second leading disease after cardiovascular disease.

The whole depression can be divided into youth type, adult type, and elderly type. Among them, the elderly group has a higher prevalence of depression, is not easy to detect, and has a high rate of missed diagnosis. The data shows that 5 of the top 10 diseases causing disability are mental disorders, and depression ranks first, which seriously affects the quality of life and social functions of the elderly.

Depression in the elderly interacts with aging and various chronic diseases, and it is difficult to separate them. Many studies have found that depression accelerates shortened telomere length, brain aging, and epigenetic phenotype aging. At the same time, depression increases the risk of obesity, frailty, diabetes, cognitive impairment and mortality. In addition, many medical diseases, including patients with cardiovascular and cerebrovascular diseases, are often accompanied by depression after diagnosis.

Researchers from Zhejiang University of Technology published an article in the journal J AFFCT DISORD saying that increasing NMN levels may be an effective treatment for depression.

Research in recent years has proposed a new perspective on "dealing" with depression: depression may not only be a neuroendocrine disease, but also a mitochondrial dysfunction disease.

Mitochondrial dysfunction can be caused by chronic stress, which affects extracellular matrix proteins and induces oxidative stress, leading to neuropathies in the brain, and depression. NMN has been shown to improve mitochondrial function in other non-depressive neurological disease studies, so NMN may be a potential depression therapeutic molecule.

The researchers measured and counted the metabolism and behavior of the three groups of mice, and found that NMN improved the energy metabolism and mitochondrial function of the depressed mice, and corrected the negative behavior of the mice.

The hippocampus is the most severely damaged brain region in depression, and its neuronal atrophy and loss of synaptic connections are pathological hallmarks of depression. The present study found that ATP concentration in the hippocampus of CORT-depressed mice was reduced, while NMN treatment significantly improved ATP production.

At the same time, in order to verify how NMN increases ATP in depressed mice, the authors also conducted further principle studies. The results show that NMN increases mitochondrial ATP production by three main principles:

1: NMN increases the concentration of NAD+ by increasing the enzyme activity of NAMPT (the rate-limiting enzyme of NAD+ synthesis);

2: NAD+ activates the histone deacetylase SIRT3, which increases the activity of GDH (glutamate dehydrogenase), IDH2 (isocitrate dehydrogenase) and other enzymes, and stimulates the most important reaction step of energy metabolism - tricarboxylic acid cycle;

3: ATP synthase (ATPase) activity is up-regulated by NMN.

In addition, the authors reversely verified this conclusion using neurons that knocked down SIRT3 (that is, reduced its function). Adding NMN to normal astrocytes can increase the concentration of NAD+, enhance the activities of NAMPT and ATPase, and increase the production of ATP. When SIRT3 was knocked down in this cell, the effect of NMN on ATP and ATPase was greatly reduced, indicating that NMN mainly increased mitochondrial ATP in neurons by activating SIRT3.

Combining the above two points, the experiment determined that the mitochondrial ATP concentration in the hippocampus of depressed mice was lower, and the use of NMN could significantly improve the ATP content and mitochondrial function.

Tag: NMN

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