Neurology Central

Could dietary pyruvate restore energy reserves in the aging brain?

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A new study from the University of Eastern Finland (Kuopio, Finland) has found that daily delivery of dietary pyruvate restores energy available to the brain in mice, and causes an increase in energetic and exploratory behaviours.

Previous research has demonstrated that the energy reserves in the brain decrease during normal aging, and also as a result of neurodegenerative disorders such as Alzheimer’s disease (AD). This new finding could hold promise of a clinical solution for re-energizing the aging brain, and to combat the effects of neurodegeneration.

The brain is a demanding drain on energy resources: in humans, it uses 20–30% of the body’s energy reserves. As we age, during the course of neurodegenerative disorders, and in times of physiological stress, the supply of sugars to the brain decreases. This causes a reduction in the energy stores available to the brain, leading to a decline in cognition and memory.

Within the new study, mice received Na-pyruvate in their food for 2–6 months. Metabolic postmortem assays revealed that this led to increased brain energy reserves in the form of glycogen, creatine and lactate in treated mice compared with a control group.

As well as improving metabolic reserves in the brain, investigators also recorded a positive change in behavior and learning in the mice as a result of the dietary pyruvate. Treated mice displayed improved spatial learning and increased exploration of a novel odour in a series of behavioral tasks.

Tanila commented: “The mice became more energetic and increased their explorative activity. It appears that these behavioral changes are directly due to the effect of pyruvate on brain function, since we didn’t find that these mice had developed greater muscle force or endurance.”

Interestingly, treated mice displayed paradoxical impairment of fear memory during a passive avoidance task. However this could be explained by the increased exploratory behavior caused by the long-term pyruvate supplement.

Importantly, experiments were repeated using both wild-type and transgenic APP/PS1 mice, which are used as an animal model for AD. These mice display the same deposition of protein plaques in the brain, neurodegeneration and cognitive decline as in people with AD. Notably, the application of dietary pyruvate yielded the same positive response in APPswe/PS1dE9 mice as it did in wild-type mice.

The team established that 800 mg / kg / day pyruvate – equivalent to approximately 10 g / day in humans – was sufficient to elicit these metabolic and behavioral changes in the mice. Notably, a single large dose of pyruvate injected directly into the bloodstream did not elicit any detectable effect.

While these findings hint that pyruvate could counteract the cognitive decline observed as a result of normal aging and neurodegenerative disorders, it should be noted that the benefit observed in treated mice was seemingly related to increased exploratory behavior rather than direct memory enhancement. Nevertheless, dietary pyruvate supplements may prove a useful aid in reducing inactivity and cognitive impairment in the aging brain.

“Pyruvate supplementation may prove beneficial as an activating treatment for the elderly and in therapies for alleviating cognitive decline due to aging, neurodegenerative disease, or mental disorders. It is well tolerated and warrants further studies in humans,” concluded Tanila.

 

Koivisto H, Leinonen H, Puurula M et al. Chronic Pyruvate Supplementation Increases Exploratory Activity and Brain Energy Reserves in Young and Middle-Aged Mice. Front. Aging Neurosci. 8(41),  doi: 10.3389/fnagi.2016.00041 (2016); Frontiers press release via EurekAlert

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