NMNNMN decreases depressive behaviour and improves energy production in the brains of mice

Fred

NMN decreases depressive behaviour and improves energy production in the brains of mice

Post by Fred » Wed Dec 11, 2019 7:45 am

"Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice"


Highlights

• Chronic CORT impairs mitochondrial energy metabolism in the hippocampus and liver.

• NMN ameliorates the depression-like behaviors induced by CORT.

• NMN can attenuate the disruption of mitochondrial energy production.

• Sirt3 knockdown in astrocytes reversed effect of NMN by reducing energy production.


Background
Nicotinamide mononucleotide (NMN) has been shown to stimulate oxidative phosphorylation in mitochondria and to improve various pathologies in patients and mouse disease models. However, whether NMN mediates mitochondrial energy production and its mechanism of action in depressed animals remain unclear.

Methods
Mice were subcutaneously injected with corticosterone (CORT; 20 mg/kg) each day for 6 weeks, while another group was given an additional dose of NMN (300 mg/kg) by oral gavage in the last 2 weeks. Then, transcriptome analyses, metabolome analyses and transient gene knockdown in primary mouse cells were performed.

Results
NMN administration alleviated depression-like behavior and the liver weight to body weight ratio in a mouse model of CORT-induced depression. Transcriptome and metabolome analyses revealed that in depressed mice, NMN reduced the mRNA expression of genes involved in fatty acid synthesis, stimulation of β-oxidation and glycolysis, and increased production of acetyl-coenzyme A for the tricarboxylic acid cycle. Importantly, NMN supplementation increased NAD+ levels to enhance sirtuin (SIRT)3 activity, thereby improving mitochondrial energy metabolism in the hippocampus and liver of CORT-treated mice. Sirt3knockdown in primary mouse astrocytes reversed the effect of NMN by inhibiting energy production, although it did not affect NAD+ synthesis

Limitations
Group sample sizes were small, and only one type of primary mouse cell was used

Conclusion
These results provide evidence for the beneficial role of NMN in energy production and suggest that therapeutic strategies that increase the level of NMN can be an effective treatment for depression

https://sci-hub.se/https%3A%2F%2Fwww.sc ... a%253Dihub


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Drdavid
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Joined: Thu Aug 15, 2019 9:59 am

Re: NMN decreases depressive behaviour and improves energy production in the brains of mice

Post by Drdavid » Wed Dec 11, 2019 9:30 pm

Fred wrote:
Wed Dec 11, 2019 7:45 am
"Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice"


Highlights

• Chronic CORT impairs mitochondrial energy metabolism in the hippocampus and liver.

• NMN ameliorates the depression-like behaviors induced by CORT.

• NMN can attenuate the disruption of mitochondrial energy production.

• Sirt3 knockdown in astrocytes reversed effect of NMN by reducing energy production.


Background
Nicotinamide mononucleotide (NMN) has been shown to stimulate oxidative phosphorylation in mitochondria and to improve various pathologies in patients and mouse disease models. However, whether NMN mediates mitochondrial energy production and its mechanism of action in depressed animals remain unclear.

Methods
Mice were subcutaneously injected with corticosterone (CORT; 20 mg/kg) each day for 6 weeks, while another group was given an additional dose of NMN (300 mg/kg) by oral gavage in the last 2 weeks. Then, transcriptome analyses, metabolome analyses and transient gene knockdown in primary mouse cells were performed.

Results
NMN administration alleviated depression-like behavior and the liver weight to body weight ratio in a mouse model of CORT-induced depression. Transcriptome and metabolome analyses revealed that in depressed mice, NMN reduced the mRNA expression of genes involved in fatty acid synthesis, stimulation of β-oxidation and glycolysis, and increased production of acetyl-coenzyme A for the tricarboxylic acid cycle. Importantly, NMN supplementation increased NAD+ levels to enhance sirtuin (SIRT)3 activity, thereby improving mitochondrial energy metabolism in the hippocampus and liver of CORT-treated mice. Sirt3knockdown in primary mouse astrocytes reversed the effect of NMN by inhibiting energy production, although it did not affect NAD+ synthesis

Limitations
Group sample sizes were small, and only one type of primary mouse cell was used

Conclusion
These results provide evidence for the beneficial role of NMN in energy production and suggest that therapeutic strategies that increase the level of NMN can be an effective treatment for depression

https://sci-hub.se/https%3A%2F%2Fwww.sc ... a%253Dihub


Image
Another great research project that seems to point to the fact that NMN can eventually be a treatment for depression. As the evidence continues to mount would should see a large scale human trial.
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daviddean
Posts: 38
Joined: Wed Aug 21, 2019 8:14 am

Re: NMN decreases depressive behaviour and improves energy production in the brains of mice

Post by daviddean » Fri Dec 13, 2019 4:47 am

Fred wrote:
Wed Dec 11, 2019 7:45 am
"Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice"


Thank you Fred for posting this interesting article.
We have discussed this topic also in another post of this Forum.
I outlined the possible correlation between mithocondrial disorders and psychiatric illness, included anxiety and depression.
I did some quotes from 2 interesting studies:

There is evidence that people with known mitochondrial disorders suffer psychiatric illness at rates higher than the general population.
A mitochondrial bioenergetic basis of depression
N. Jennifer Klinedinst & William T. Regenold
Link: https://www.ncbi.nlm.nih.gov/pubmed/25262287

Here is another intesting study, more specific the depression and mitochondrial disorders.
Brain is highly active organ with high energy consumption and organs with highest energy demand are more susceptible to the deleterious effect of reduced energy production. Mainly neurons obtain energy from mitochondrial OXPHOS. Neuron obtains energy through glycolysis but brain is unable to store glycogen so constant supply of glucose is needed. When oxidative phosphorylation is compromised, neurons are unable to meet their energy demand and alteration in their various physiological functions occurs due to reduced ATP production. Studies have shown that chronic mild stress inhibits mitochondrial OXPHOS, dissipates mitochondrial membrane potential and damages mitochondrial ultrastructure in various brain regions including hippocampus, cortex and hypothalamus of mice [77, 78]. These observations lead to the conclusion that most probably depression is caused by energy impairment in the brain due to mitochondrial dysfunction [79, 80].

Mitochondrial Dysfunction in Depression
Yashika Bansal and Anurag Kuhad
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981740/


In my personal experience, using Alybe by Nature NMN sublingual, I assume 8 tablets daily and I can affirm a mood more stable, no more depression symptoms, rare anxiety and, above all, an improved mental and physical energy. I'm 50 now and for me it works well.
David

We can reread it here:
viewtopic.php?f=7&t=1242
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