Every cell in our body needs energy to survive. This energy is supplied by 'energy factories' within cells, known as 'mitochondria'. Of all the cells in the body, our brain cells are among the most reliant on mitochondria, because brain cells work at the limits of energy availability. If you think about how you struggle to think when you are experiencing a 'sugar low' and your mind feels sharper as soon as you eat something, you will realise just how powerful this dependence on energy supply is. If a brain cell is ever struggling to survive, it can put up a better fight if it has healthy mitochondria that provide it with plenty of energy.Mitochondria give a nerve cell the ability to be resilient.
Two recent discoveries in the medical field take this feature of mitochondria to a whole new level.
1. The ‘tails’ or ‘axons’ of our nerve cells are covered in a sheath known as ‘myelin’. Nerves need their myelin. If a nerve cell's axon loses its myelin, the nerve cell might die. Recent studies suggest that this vulnerability might be overcome with healthy mitochondria. Nerve cells with healthy mitochondria seem to be able to survive, despite losing their myelin. This has huge implications for the disease multiple sclerosis, where nerves become ‘demyelinated’.
2. Glaucoma is one of the commonest causes of blindness around the world. A high pressure within the eyeball causes mechanical trauma to the optic nerve which results in blindness. Lately, we have come to realize that there is a missing link somewhere, since the relationship between blindness and raised pressures within the eyeball is actually not straightforward. It seems that a retinal nerve ‘cell’ that is exposed to high pressures could still survive – healthy mitochondria may be the determining factor. The nerve cells of people with healthy mitochondria seem to resist the assault caused by high pressures. The cells of people with ‘unhealthy’ mitochondria seem unable to resist the assault and may ‘die’.
Alcohol and mitochondria
It’s a well known fact that when we get a little tipsy, we might have a problem walking in a straight line. Walking heel-to-toe can be particularly difficult. These signs are typical of a malfunctioning cerebellum, the part of the brain responsible for balance and co-ordination. One recent study has shown the cerebellum may also have a role to play in depression.
It appears that if we make mice get a hangover from drinking alcohol and then look at the mitochondria within the cerebellum, we find that the alcohol has made the mitochondria malfunction. Alcohol also increases levels of ‘toxic agents’ (free radicals:hydrogen peroxide) that cause wear-and-tear damage to mitochondria over time. This effect of alcohol is also seen in other parts of the brain, such as in the cortex.
Alcohol may cause inflammation within the brain through this route. Much of the damage alcohol inflicts on the liver is thought to be through its effect on the mitochondria of liver cells.
The hippocampus region of the brain is the part of the ‘logical’ brain circuit that plays a vital role in learning and memory. In rats, chronic alcoholism specifically damages the hippocampus. The brain cells within the hippocampus show mitochondrial swelling and damage. Binge drinking can irreversibly impair some aspects of memory ...now you know why!
The prefrontal cortex is responsible for rational thought, logic, problem-solving and other aspects of executive function. There is a molecule that plays a role in cell death called ‘Krüppel-like factor 11’ (KLF11) which is raised within identical parts of the brain (the prefrontal cortex and the hippocampus = the ‘rational’ brain circuit) in the setting of both chronic stress and exposure to alcohol.
The hippocampus is known to ‘shrink’ with chronic stress and in the setting of depression. You can see how drinking too much alcohol has the potential to lead to the same brain changes found in depression, stress and burnout, probably through the effect of alcohol on mitochondria. Drinking too much while experiencing a lot of stress may be the worst combination for your brain – and for your mental performance.
Alcohol seems to damage mitochondria. Every brain cell is highly dependent on its mitochondria. Healthy mitochondria permit healthy brain cells. Healthy brain cells enhance mental performance and resist the effects of ageing and stress.
So, for a sharp mind and healthy mitochondria, you might want to limit your alcohol intake. We do not have enough data to be able to say exactly how much alcohol one may drink before mitochondrial damage becomes considerable. Studies so far suggest that at the very least it is best not to binge drink or drink amounts that leave you with a hangover. When you are feeling stressed, try to resist the urge to soothe your nerves with a glass of wine and ....go for a run instead!
Kiryu-Seo S1, Ohno N, Kidd GJ, Komuro H, Trapp BD. Demyelination increases axonal stationary mitochondrial size and the speed of axonal mitochondrial transport. Journal of Neuroscience, vol. 30, no. 19, pp. 6658–6666.
Pathak D, Shields LY, Mendelsohn BA, Haddad D, Lin W, Gerencser AA, Kim H, Brand MD, Edwards RH, Nakamura K. The Role of Mitochondrially Derived ATP in Synaptic Vesicle Recycling. Journal of Biological Chemistry, 2015; 290 (37): 22325
Lascaratos G, Chau KY, Zhu H, Gkotsi D, King R, Gout I, Kamal D, Luthert PJ, Schapira AH, Garway-Heath DF. Resistance to the most common optic neuropathy is associated with systemic mitochondrial efficiency. Neurobiol Dis. 2015 Jun 6;82:78-85.
Karadayian AG, Bustamante J, Czerniczyniec A, Lombardi P, Cutrera RA, Lores-Arnaiz S. Alcohol hangover induces mitochondrial dysfunction and free radical production in mouse cerebellum. Neuroscience. 2015 Sep 24;304:47-59.
Schutter DJ. A Cerebellar Framework for Predictive Coding and Homeostatic Regulation in Depressive Disorder. Cerebellum. 2015 Aug 7.(Epub ahead of print)
Bustamante J, Karadayian AG, Lores-Arnaiz S, Cutrera RA. Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover. Alcohol. 2012 Aug;46(5):473-9.
Hanamsagar R., Torres V., Kielian T. (2012). Inflammasome activation and IL-1β/IL-18 processing are influenced by distinct pathways in microglia. J. Neurochem. 119 736–748
Alfonso-Loeches S, Ureña-Peralta JR, Morillo-Bargues MJ, Oliver-De La Cruz J, Guerri C. Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome activation and cell death in astroglial cells. Front Cell Neurosci. 2014 Aug 1;8:216.
Bonet-Ponce L, Saez-Atienzar S, da Casa C, Flores-Bellver M, Barcia JM, Sancho-Pelluz J, Romero FJ, Jordan J, Galindo MF. On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response. Biochim Biophys Acta. 2015 Jul;1852(7):1400-9.
Du A, Jiang H, Xu L, An N, Liu H, Li Y, Zhang R. Damage of hippocampal neurons in rats with chronic alcoholism. Neural Regen Res. 2014 Sep 1;9(17):1610-5.
Song BJ, Akbar M, Abdelmegeed MA, Byun K, Lee B, Yoon SK, Hardwick JP. Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications. Redox Biol. 2014;3:109-23. Review.
Duncan J, Wang N, Zhang X, Johnson S, Harris S, Zheng B, Zhang Q, Rajkowska G, Miguel-Hidalgo JJ, Sittman D, Ou XM, Stockmeier CA, Wang JM. Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain. Neurotox Res. 2015 Jul;28(1):18-31.
Cippitelli A, Zook M, Bell L, Damadzic R, Eskay RL, Schwandt M, Heilig M. Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats. Neurobiol Learn Mem. 2010 Nov;94(4):538-46.