Why do we feel listless when we are recovering from an illness? The answer is, apparently, that chronic low-grade inflammation interferes with the dopamine signaling system in the brain that motivates us to do things. This was reported by studies conducted at Emory University, which explain the links between the presence of an inflammatory reaction in the body, the reduced release of dopamine in the brain, and the motivation to do things. They also present the possibility that this is part of the body’s effort to optimize its energy expenditure during inflammation. The underlying hypothesis is that the body needs more energy to heal a wound or to get over an infection, for example, both of which are associated with low-grade inflammation. To ensure that energy is available, the brain uses an adaptive technique to reduce the natural urge to perform other tasks that could potentially drain the energy needed for healing.
This is essentially a recalibration of the specialized reward neurons in the brain’s motivation center so that ordinary activities no longer seem worth living. According to the research, the mechanism of this recalibration is mediated by the immune system. The computational technique published by the scientists is designed to allow for experimental measurements of the extent to which low-grade inflammation affects the amount of energy available and the decision to do something based on the effort required. This may allow us to better understand why and how chronic inflammatory states cause a lack of motivation in other conditions as well, including schizophrenia and depression. It is already known that immune cells release cytokines, which affect the functioning of neurons that release dopamine in the area of the brain called the mesolimbic system. This area enhances our willingness to work hard for a reward.
Recently, it has been found that immune cells also enjoy a unique ability to move between various metabolic states, unlike other cells. This could affect cytokine release patterns in a way that signals the brain to conserve energy available for use by the immune system. These facts were the foundation of the new hypothesis, which is explained in terms of evolutionary adaptation. In the hypothetical environment of prehistoric man, the immune system, faced with abundant microbial and predatory challenges, needed enormous amounts of energy. It therefore had its own mechanism for signaling other systems in the body, via the mesolimbic system, to control the use of energy resources during times when the organism was experiencing severe or sudden stress. Modern life is relatively smooth and less demanding. With less physical activity, low-grade inflammation is mainly due to lifestyle factors such as chronic stress, alcohol abuse, smoking and overeating.
This could mistakenly cause mesolimbic dopamine neurons to produce less dopamine. Low dopamine levels in turn decrease motivation to work, reducing the perception of reward and increasing the perception of effort involved. This eventually conserves energy for use by the immune system. Even a newly published study by MIT scientists confirmed that a cell group in the brain striatum encodes information about the potential outcomes of several decisions. These neurons become especially active when behavior leads to a different outcome than expected, which researchers say helps the brain adapt to changing circumstances. Previous studies have shown that high immune functioning associated with low dopamine levels and reduced motivation characterize some forms of schizophrenia, depression and other mental health conditions. Scientists do not believe that these disorders are caused by low-grade inflammation,
Rather, that some people who have these diseases are hypersensitive to immune cytokines. This could in turn cause them to lose motivation for everyday life. Scientists do not believe that inflammation causes these mental health disorders for all individuals taken collectively. The idea is that a subset of people with these disorders may have a particular sensitivity to the effects of the immune system and this sensitivity could contribute to the motivational impairments they are experiencing. These scientific implications, however, have another outcome: to make us reflect on what is good or bad for our health, for example. All the wrong lifestyles are accepted normally and it is often difficult to give up bad food choices, the addiction of smoking or alcohol. The question therefore is: “the wrong external stimuli cause areas of the brain such as the striatum to inflame, which will affect my willpower?”
If this theory proves correct, then it could have a huge impact on treating cases of depression and other behavioral disorders with underlying inflammation. It would open up opportunities for the development of therapies that target the use of energy by immune cells, instead of those traditionally aimed at suppressing them through immunosuppressive drugs such as cortisone. But it could provide information on how to better orient personal choices of every day, from those at the table to those at work, to choose a drug addiction, up to saying “this cigarette is not good for my health” or “something will have to be dying for”.
- A cura del Dr. Gianfrancesco Cormaci, PhD, specialista in Biochimica Clinica.
Brain Behav Immun Health. 2021 Feb 13:100226.
Treadway MT et al. Trends Cogn Sci. 2019 May; 23(5):435-448.
Felger JC et al. Neuropsychopharmacol. 2017; 42(1):216-241.
Hosking JG et al. Neuropsychopharmacol. 2015; 40(4):1005-15.
Dott. Gianfrancesco Cormaci
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