Why take smart drugs when you can instead fix ‘struggling’ energy factories to enhance brain functio


Two studies on the brain made headline news this week and although the popular media did not link them, they are essentially two sides of the same coin. One study was about 'smart drugs' and the other was on why some brain cells succumb to Parkinson's Disease.

'Mitochondria' are the little energy factories inside cells. They need to keep providing energy for a cell to survive and function. If you look at what happens across the full spectrum of mitochondrial dysfunction, at the milder end you might find a cell 'slows down' whereas at the more severe end, you might find cells die.

Hypothetically, if our brain cells were to start 'slowing down' as we entered into our 30s, 40s and 50s from mild mitochondrial dysfunction, smart drugs might have some effect in bringing our cognitive performance back up. On the other hand, if our brains continued to be deprived of energy from poorly functioning mitochondria in the longer term, this would put us at risk of developing neurodegenerative diseases, such as Parkinson's Disease. The reason why we might reach for smart drugs and why we might develop Parkinson's Disease are linked, through the action of mitochondria.

When we speak of wear and tear of the brain, we often refer to the wear and tear taking place within the brain cells’ mitochondria. As those cells and their mitochondria work at breaking down glucose to produce energy, this process produces ‘oxidative stress’ which causes wear and tear damage. This is why we are constantly told to take anti-oxidants. Brain cells that produce energy at a faster rate also accumulate more wear and tear damage. This is where our first headlining scientific study from this week comes in.

Parkinson’s Disease is a debilitating neurodegenerative disease that affects a very select group of brain cells sitting in a particular part of the brain, which depend on the neurotransmitter ‘dopamine’.

This week, a research team has shown that when compared with other brain cells, these cells appear to have:

  • a ‘smaller reserve capacity’ [meaning less ‘extra’ energy]

  • a higher basal rate of mitochondrial OXPHOS [meaning mitochondria are having to work faster]

  • an elevated level of basal oxidative stress [meaning more wear and tear damage]

This excessive pressure on the mitochondria to produce more energy may be making the brain cells more vulnerable to degeneration as the mitochondria are getting 'worn out'. The authors of the study propose this might be a possible reason behind why Parkinson’s affects only this very specific group of brain cells.

We know that mitochondria struggle with energy production for a while before neurodegenerative disease sets in. Some medical researchers are trying to find out if this struggle is what gives rise to neurodegenerative diseases in the first place.

We also know that as we grow older, even in the absence of disease, mitochondria start to struggle with using glucose as fuel. We think that as they suffer increased wear and tear damage, they might start finding it more difficult to use glucose for fuel and using an alternative fuel source, such as ketones, might 'reduce the workload'. Ketones have also been shown to increase mitochondrial numbers. There remains a possibility that offering brain cells an alternative source of fuel could counter mitochondrial dysfunction and even hold off neurodegeneration.

It may be that our brain cells start to struggle with wear and tear damage to mitochondria while we are still in our prime and long before we think of ourselves as 'old'. It may also be that this ‘struggle’ affects brain performance.

Stress may play an important role here. A recent study has suggested that Post Traumatic Stress Disorder (PTSD) may have an effect on mitochondrial growth and function (though more work is needed to confirm this). If stress does turn out to contribute to mitochondrial dysfunction, then those of us who experience a great deal of stress may be more susceptible to reduced mitochondrial energy production and our brains may not be receiving the energy we would expect. If the compromise in energy supply affects our cognitive function then we might seek out ways to further enhance our cognitive performance.

Enter our second headlining study of the week.

Drugs that supposedly make our brains ‘sharper’ seem to be gaining popularity, particularly amongst people in stressful and intellectually-demanding jobs. Some of these ‘Nootropics’ or ‘smart drugs’ are legal whereas others are not. Tea and coffee may be seen as 'legal' smart drugs. Most of today’s newer smart drugs were developed to enhance brain function in patients with neurodegenerative diseases such as Alzheimer’s Disease, but their effects are also attractive to the healthy population.

This week, a study on the smart drug Modafinil made headlines when it confirmed that Modafinil does indeed enhance cognition. We still do not fully understand exactly how Modafinil works. We know it affects neurotransmitters within the brain, including the neurotransmitter ‘dopamine’ (interestingly Modafinil has been investigated in Parkinson’s Disease). Since we do not fully understand how Modafinil works, we also do not know its full range of undesirable effects.

In general, agents that enhance cognitive performance often do so only if performance is not at an optimum level. Even more interestingly, many smart drugs work by enhancing mitochondrial function.

Some of our brain cells may be suffering from energy deprivation when we hit middle-age (or sooner). This energy deprivation may partly stem from brain cells not being able to process glucose for energy very well, any more. Stress may play a role. Our brain feels ‘sharper’ when we are young and have not been battered by years of stressful work and experiences.

If we can correct this energy dysfunction, we might be able to achieve the same effects a taking a smart drug and even ward off neurodegeneration in the future, without the need to reach for a single smart drug. Delivering an alternative fuel to the brain (ketones) through dietary changes may maintain energy supply. Other studies suggest certain alterations in our diet might reduce mitochondrial oxidative damage (wear and tear damage). Particular lifetyle and dietary changes can turn on pathways that lead to increased mitochondrial numbers and health. It seems that mitochondrial health may play a pivotal role in brain function and long term health.

Instead of looking towards temporary solutions with smart drugs we should pursue longer-term strategies for preventing mitochondrial dysfunction. The smart drug Modafinil and the revelations about Parkinson’s Disease seem to be two sides of the same coin – that of mitochondrial health. Mitochondrial health may be the holy grail for optimising brain performance while at the same time safeguarding our brains from various forms of neurodegeneration in the future.

N.B.

This site is for discussion only and should not be used as a source of medical information. Please consult your medical doctor before making any changes to your diet, lifestyle or medications.

References

Bersani FS, Morley C, Lindqvist D, Epel ES, Picard M, Yehuda R, Flory J,

Bierer LM, Makotkine I, Abu-Amara D, Coy M, Reus VI, Lin J, Blackburn EH, Marmar C, Wolkowitz OM, Mellon SH. Mitochondrial DNA copy number is reduced in male combat veterans with PTSD. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jun 26;64:10-17.

Consiglia Pacelli, Nicolas Giguère, Marie-Josée Bourque, Martin Lévesque, Ruth S. Slack, Louis-Éric Trudeau. Elevated Mitochondrial Bioenergetics and Axonal Arborization Size Are Key Contributors to the Vulnerability of Dopamine Neurons. Current Biology, 2015; DOI: 10.1016/j.cub.2015.07.050

Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR. Oxidative stress and Parkinson's disease. Front Neuroanat. 2015 Jul 8;9:91.

Lökk J. Daytime sleepiness in elderly Parkinson's disease patients and treatment with the psychostimulant modafinil: A preliminary study. Neuropsychiatr Dis Treat. 2010 Apr 7;6:93-7.

Ornell F, Valvassori SS, Steckert AV, Deroza PF, Resende WR, Varela RB, Quevedo J. Modafinil effects on behavior and oxidative damage parameters in brain of wistar rats. Behav Neurol. 2014;2014:917246

R.M. Battleday, A-K. Brem. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: a systematic review. European Neuropsychopharmacology, 2015; DOI: 10.1016/j.euroneuro.2015.07.028

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