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Oxidative stress affects motivation, but diet can help

Oxidative stress affects motivation, but diet can help

Summary: Higher levels of glutathione in the nucleus accumbens correlate with better and more stable performance in motivational tasks. The findings suggest that improvements in accumbal antioxidant function that can be obtained through diet or supplementation may be a feasible approach to enhance motivation.

Source: EPFL

In life, motivation can be the difference between success and failure, goal setting and aimlessness, prosperity and misfortune. Yet getting and staying motivated is often the hardest step, a problem that has fueled much research.

Very little of that research dealt with the issue of metabolism. “Do differences in brain metabolites affect our ability to motivate?” asks Professor Carmen Sandi at EPFL’s School of Natural Sciences. “If this is the case, would nutritional interventions that can affect metabolite levels be an effective means of improving motivated performance?”

Sandi’s group, with colleagues at the Nestlé Institute of Health Sciences, has published a study that sheds the first light on the answer to that question. The researchers focused on an area deep in the brain called the nucleus accumbens, which is known to play a major role in regulating functions such as reward, reinforcement, aversion, and not least, motivation.

Metabolism and oxidative stress in the brain

The idea behind the study was that the brain itself – like all tissues in our body – is subjected to constant oxidative stress, as a result of its metabolism.

What is oxidative stress? As cells “eat” various molecules for fuel, they produce numerous toxic waste products in the form of highly reactive molecules collectively known as “oxidative species”. Naturally, cells have a number of mechanisms to remove oxidative species, restoring cellular chemical balance. But that battle is ongoing, sometimes that balance is disturbed and that disturbance is what we call “oxidative stress”.

Glutathione binding

The brain is then often exposed to excessive oxidative stress due to its neurometabolic processes – and the question for the researchers was whether antioxidant levels in the nucleus accumbens could affect motivation. To answer the question, scientists looked at the brain’s most important antioxidant, a protein called glutathione (GSH), and its connection to motivation.

“We assessed the relationships between metabolites in the nucleus accumbens—a key brain region—and motivated performance,” says Sandi. “We then turned to animals to understand the mechanism and examine the causality between the metabolite found and the effect, also proving that nutritional interventions modify behavior through this pathway.”

Monitoring of GSH in the nucleus accumbens

First, they used a technique called “proton magnetic resonance spectroscopy,” which can assess and quantify biochemistry in a specific brain region in a non-invasive way.

The researchers applied the technique to the nucleus accumbens of both humans and rats to measure GSH levels. They then compared those levels to how well or poorly their humans and animals performed on standardized effort-related tasks that measure motivation.

What they found was that higher levels of GSH in the nucleus accumbens correlated with better and more stable performance on motivational tasks.

GSH levels and motivation

But correlation does not imply causation, so the team moved on to live experiments with rats given microinjections of GSH blockers, reducing antioxidant synthesis and levels. The rats now showed less motivation, as reflected by poorer performance in effort-based and reward-based tests.

This shows the salmon
Cysteine ​​is found in ‘protein-rich foods’, such as meat, chicken, fish or seafood. Image is in the public domain

On the contrary, when the researchers gave the rats a nutritional intervention with the GSH precursor N-acetylcysteine—which increased GSH levels in the nucleus accumbens—the animals did better. The effect is “potentially mediated by a cell type-specific shift in glutamatergic inputs to accumbal medium spiny neurons,” the authors write.

Can nutrition or supplements help with motivation?

“Our study provides new insights into how brain metabolism is linked to behavior and suggests nutritional interventions targeting key oxidative processes as ideal interventions to facilitate endurance,” the authors conclude. The study’s findings “suggest that improving accumbal antioxidant function may be a feasible approach to enhancing motivation.”

“N-acetylcysteine, the dietary supplement we provided in our study, can also be synthesized in the body from its precursor cysteine,” says Sandi. “Cysteine ​​is found in ‘protein-rich foods’ such as meat, chicken, fish or seafood. Other sources with lower content are eggs, whole grain foods like breads and cereals, and some vegetables like broccoli, onions and legumes.”

“Of course, there are ways other than N-acetylcysteine ​​to increase GSH levels in the body, but how they relate to levels in the brain—and specifically in the nucleus accumbens—is largely unknown. Our study provides proof of principle that dietary N-acetylcysteine ​​can increase GSH levels in the brain and facilitate effortful behavior.”

See also

This shows the outline of the head

About this motivation and news about neuroscience research

Author: Press Office
Source: EPFL
Contact: Press Office – EPFL
picture: Image is in the public domain

Original Research: Open access.
Glutathione in the nucleus accumbens regulates motivation to exert reward-driven effort”, by John Zalachoras et al. eLife


Abstract

Glutathione in the nucleus accumbens regulates motivation to exert reward-driven effort

New evidence implicates mitochondrial function and metabolism in the nucleus accumbens in motivated performance.

However, the brain is sensitive to excessive oxidative insults resulting from neurometabolic processes, and it is unknown whether antioxidant levels in the nucleus accumbens contribute to motivated performance.

Here we identify the key role of glutathione (GSH), the most important endogenous antioxidant in the brain, in motivation.

Using proton magnetic resonance spectroscopy (1H-MRS) at ultra-high field in both clinical and preclinical populations, we found that higher accumbal GSH levels significantly predicted better and particularly stable performance over time in effort-related tasks.

Causality was established in preclinical in vivo experiments that, first, showed that depletion of GSH levels through microinjections of the GSH synthesis inhibitor buthionine sulfoximine into the nucleus accumbens impairs reward-based performance.

In addition, systemic treatment with the GSH precursor N-acetyl-cysteine ​​(NAC) increased accumbal GSH levels and led to improved performance, potentially mediated by a cell type-specific shift in glutamatergic inputs to accumbal medium spiny neurons. Our data indicate a close relationship between accumbal GSH levels and an individual’s ability to exert reward-induced effort over time.

They also suggest that improving accumbal antioxidant function may be a feasible approach to enhancing motivation.



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