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"Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome" by Bjorklund et. al.
January 10, 2022 Chronic Fatigue Syndrome and Exposure to Ionizing Radiation"It has been established that radiation exposure in the low-dose range (less than 0.5 Gy) can lead to dysfunctions of the autonomic nervous system, asthenic manifestations, back pain, arthralgia, symptoms of encephalopathy, myelopathy, and somatoform disorders [61, 62]. For example, these manifestations were observed in the liquidators of the Chernobyl accident, who often met the CFS criteria [63, 64]. There is some evidence that CFS due to radiation factor exposure may be explained by the imbalance among endocrine, immune, and basic regulatory systems, such as the autonomic nervous system, along with psychogenic effects associated with radiophobia [65–67]. Mental disorders, also relevant to CFS, were found in the War veterans in the Persian Gulf and the Balkans. The onset of these symptoms could be caused by the effect of depleted uranium used to create armor-piercing ammunition and military equipment [68, 69]. In the first 5–6 years after the Chernobyl nuclear power plant accident, endocrine disorders in the form of hypercortisolemia, hyperinsulinemia, and increased production of growth hormone and estradiol; decrease in the level of testosterone and endorphins were diagnosed in the liquidators. These disorders were considered to be manifestations of radiation-induced stress and post-radiation compensatory stress, which could later lead to organ pathologies, including diabetes mellitus, arterial hypertension, and coronary heart disease [70, 71]. A Ukrainian study included 367 liquidators of the Chernobyl accident and found that since 1990, the prevalence of CFS decreased from 65.5 to 10.5% (p < 0.01) over the course of 10 years. However, the prevalence of metabolic syndrome increased over this period, from 15.0 to 48.2% (p < 0.01), and 26% of the CFS included in the study remained in the same condition, while 48.0% of the cases developed metabolic syndrome.Overall, in 26% of the studied individuals, CFS transformed into another somatic pathology. Interestingly, the authors concluded that CFS and metabolic syndrome are different stages of the same systemic pathology associated with ionizing radiation and stressful psychogenic effects [72]. Some authors have linked manifestations of radiation-induced CFS in Chernobyl accident clearance workers with identified cognitive impairment and EEG changes. The study of bio-electric activity showed a shift in the EEG from an organized to an unorganized pattern, as well as an increase in the spectral d-power in the left frontotemporal region [73]. The pathogenesis of the latter condition includes the combined effect of a genetic predisposition and environ-mental factors leading to functional disorders in neuro-immune-hormonal axes, including dysfunction of the nervous system causing immune disorders and decreased activity of the sympathoadrenal system, basal levels of vasopressin, and renin activity, manifesting itself in hypotensive reactions. The radiation factor and the psychogenic effects caused by the ecological situation can lead to prolonged oxidative stress, characterized by activation of free radical oxidation and inhibition of antioxidant activity [74, 75]. Disorders of hormone-receptor interaction in the liquidators of the Chernobyl accident can be caused by an increase in the microviscosity of erythrocytes and leukocytes membranes, loosening of membrane proteins, and the release of tryptophanyls on their surface. Small doses of radiation may cause disturbances in the permeability of biological membranes, decrease in the activity of membrane enzymes, impaired ability to bind receptors to their signal molecules, and decrease in the ratio of cyclic adenosine monophosphate/phosphodiesterase. Thus, oxidative stress leads to adverse changes in the system of neuro-humoral regulation [76]. Free radical peroxidation of polyenes in biological membranes can lead to destabilization of ion channel structures even at low-dose irradiation. The cleavage of peptides may cause immediate closure and damage to the function of ion channels while increasing the flow of calcium into skeletal muscle cells. This leads to the development of fibromyalgia symptoms typical for CFS [77]. Damage to mitochondrial DNA (mDNA) is also considered as one of the critical mechanisms of radiation effects. The mitochondrial genome is characterized by significant instability since the rate of mDNA replication is 10–20 times higher than that of nuclear DNA due to pronounced redox processes. Mitochondrial DNA is particularly sensitive to oxidation and is, therefore, the target of ionizing radiation even in cells with low proliferative activity. CFS is characterized by mDNA deletions in skeletal muscle accompanied by a decrease in the activity of mitochondrial enzymes. Mitochondrial dysfunction is associated with a decrease in energy production and the subsequent symptoms of CFS [78, 79]. Another theory explaining the development of radiation-induced CFS is an increase in the level of nitric oxide due to the activation of the transcription factor NF-kappa-B and nitricoxide synthase. The clinical symptoms of post-radiation syndrome are identical to those in CFS [80]. Thus, ionizing radiation is a possible cause of hypothalamic dysfunctions leading to disruption of the hypothalamus-pituitary-adrenal interactions and damage due to redox processes associated with glucocorticoid action. These processes may lead to the development of systemic radiation syndromes, which include CFS [81]." |
