Relationships between plasma levels of nitrogenous metabolites and some psycho-neuro-endocrine parameters
DOI:
https://doi.org/10.12775/JEHS.2022.12.06.036Keywords
plasma bilirubin, uric acid, urea, creatinine, cortisol, testosterone, aldosterone, triiodothyronine, calcitonin, ongoing EEG, HRV, anxiety, men, women, relationshipsAbstract
Background. It was recently shown by our group that bilirubin has a neurotropic activity. It is also shown that endogenous uric acid exerts a noticeable modulating effect on neuro-endocrine adaptation factors. In this study, we supplemented the constellation both of subjects of influence with other nitrogenous metabolites - urea and creatinine, and the objects of influence - with plasma levels of the main adaptation hormones and the severity of trait and reactive anxiety. Materials and Methods. The object of observation were almost healthy volunteers: 30 females (30÷76 y) and 31 males (24÷69 y). In basal conditions determined plasma levels of nitrogenous metabolites as well as cortisol, aldosterone, testosterone, triiodothyronine and calcitonin, estimated the severity of the trait and reactive anxiety, recorded the ongoing HRV and EEG. After 4 or 7 days, repeated testing was performed. Results. By constructing regression models, it was found that direct bilirubin determines the levels of psycho-neuro-endocrine parameters by 66,0%, free bilirubin by 56,7%, uric acid by 40,8%, creatinine by 37,6%, and urea - by 31,1%. Taken together, nitrogenous plasma metabolites determine the severity of trait, but not reactive anxiety, plasma levels of testosterone, cortisol and triiodothyronine, but not calcitonin and aldosterone, as well as a number of HRV and EEG parameters by 70,6%. Conclusion. Nitrogenous plasma metabolites, even in the absence of uremia, are able to influence the state of the psyche, autonomic and central nervous and endocrine systems, apparently through aryl hydrocarbon and adenosine receptors of neurons and endocrinocytes and/or directly.
References
Akselrod S, Gordon D, Ubel FA, Shannon DC, Barger AC, Cohen RJ. Pоwer spectrum analysis rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science (NY). 1981; 213(4504): 220-222.
Ascherio A, Chen H, Schwarschild MA, Zhang SM, Colditz GA, Speizer FE. Caffeine, postmenopausal estrogen, and risk of Parkinson's disease. Neurology. 2003; 60: 790–795.]
Ascherio A, Weisskopf MG, O'Reilly EJ, McCullough ML, Calle EE, Rodriguez C, Thun MJ. Coffee consumption, gender, and Parkinson's disease mortality in the cancer prevention study II cohort: the modifying effects of estrogen. Am J Epidemiol. 2004; 160(1): 977–984.
Babelyuk VYe, Dubkowa GI, Korolyshyn TA, Holubinka SM, Dobrovol’s’kyi YG, Zukow W, Popovych IL. Operator of Kyokushin Karate via Kates increases synaptic efficacy in the rat Hippocampus, decreases C3-θ-rhythm SPD and HRV Vagal markers, increases virtual Chakras Energy in the healthy humans as well as luminosity of distilled water in vitro. Preliminary communication. JPES. 2017; 17(1): 383-393.
Baevskiy RM, Ivanov GG. Heart Rate Variability: theoretical aspects and possibilities of clinical application. Ultrazvukovaya i funktsionalnaya diagnostika. 2001; 3: 106-127. [in Russian].
Baptista AF, Maciel ABR, Okano AH, Moreira A, Campos ACP, Fernandes AM, et al. Neuromodulation and inflammatory reflex: Perspectives on the use of non-invasive neuromodulation in the management of disorders related to COVID-19. Preprint. 2020. May: 31.
Benarroch EE. The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc. 1993; 68(10): 988-1001.
Berntson GG, Bigger JT jr, Eckberg DL, Grossman P, Kaufman PG, Malik M, Nagaraja HN, Porges SW, Saul JP, Stone PH, Van der Molen MW. Heart Rate Variability: Origines, methods, and interpretive caveats. Psychophysiology. 1997; 34: 623-648.
Bombushkar IS, Gozhenko AI, Badiuk NS, Smagliy VS, Korda MM, Popovych IL, Blavatska OM. Relationships between parameters of uric acid metabolism and neuro-endocrine factors of adaptation [in Ukrainian]. Herald of marine medicine. 2022; 2(95): 59-74.
Buzsaki G. Theta oscillations in the hippocampus. Neuron. 2002; 33: 325–340.
Carnevali L, Koenig J, Sgoifo A, Ottaviani C. Autonomic and Brain Morphological Predictors of Stress Resilience. Front Neurosci. 2018; 12: 228.
Carnevali L, Pattini E, Sgoifo A, Ottaviani C. Effects of prefrontal transcranial direct current stimulation on autonomic and neuroendocrine responses to psychosocial stress in healthy humans. Stress. 2020; 23(1): 26-36.
Chen WC, Chang LH, Huang SS, Huang YJ, Chih CL, Kuo HC, Lee YH, Lee IH. Aryl hydrocarbon receptor modulates stroke-induced astrogliosis and neurogenesis in the adult mouse brain. J Neuroinflamm. 2019; 16: 187.
Chen Y, Xu L, Xie HQH, Xu T, Fu H, Zhang S, Sha R, Xia Y, Zhao B. Identification of differentially expressed genes response to TCDD in rat brain after long-term low-dose exposure. J Environ Sci. 2017; 62: 92–99.
Dani C, Pratesi S, Ilari A, Lana D, Giovannini MG, Nosi D, Buonvicino D, Landucci E, Bani D, Mannaioni G, Gerace E, et al. Neurotoxicity of Unconjugated Bilirubin in Mature and Immature Rat Organotypic Hippocampal Slice Cultures. Neonatology. 2019; 115(3): 217-225.
Del Valle-Mondragón L, Becerra-Luna B, Cartas-Rosado R, et al. Correlation between Angiotensin Serum Levels and Very-Low-Frequency Spectral Power of Heart Rate Variability during Hemodialysis. Life (Basel). 2022; 12(7): 1020.
Efroimson VP. Some biological factors of mental activity [in Russian]. VIET. 1987; 4: 74-84.
Eckers A, Jakob S, Heiss C, Haarmann-Stemmann T, Goy C, Brinkmann V, Cortese-Krott MM, Sansone R, Esser C, Ale-Agha N, et al. The aryl hydrocarbon receptor promotes aging phenotypes across species. Sci Rep. 2016; 6: 19618.
Goryachkovskiy АМ. Clinical Biochemistry. Odesa: Astroprint; 1998: 608. [in Russian].
Gozhenko АІ, Korda MM, Popadynets’ OO, Popovych IL. Entropy, Harmony, Synchronization and their Neuro-endocrine-immune Correlates. Odesa. Feniks; 2021: 232. [in Ukrainian].
Grabert K, Michoel T, Karavolos MH, Clohisey S, Baillie JK, Stevens MP, Freeman TC, Summers KM, McColl BW. Microglial brain region-dependent diversity and selective regional sensitivities to aging. Nat Neurosci. 2016; 19: 504–516.
Guo CC, Sturm VE, Zhou J, Gennatas ED, Trujillo AJ, Hua AY, et al. Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia. Proc Natl Acad Sci USA. 2016; 113: E2430–E2439.
Heart Rate Variability. Standards of Measurement, Physiological Interpretation, and Clinical Use. Task Force of ESC and NASPE. Circulation. 1996; 93(5): 1043-1065.
Iseger TA, Padberg F, Kenemans JL, Gevirtz R, Arns M. Neuro-Cardiac-Guided TMS (NCG-TMS): Probing DLPFC-sgACC-vagus nerve connectivity using heart rate - First results. Brain Stimul. 2017; 10(5): 1006-1008.
Iseger TA, van Bueren NER, Kenemans JL, Gevirtz R, Arns M. A frontal-vagal network theory for Major Depressive Disorder: Implications for optimizing neuromodulation techniques. Brain Stimul. 2020; 13(1): 1-9.
Ivassivka SV, Popovych IL, Aksentiychuk BI, Flyunt IS. Physiological Activity of Uric Acid and its Role in the Mechanism of Action of Naftussya Water [in Ukrainian]. Kyїv. Computerpress; 2004: 163.
Keshavarzi M, Khoshnoud MJ, Ghaffarian Bahraman A, Mohammadi-Bardbori A. An Endogenous Ligand of Aryl Hydrocarbon Receptor 6-Formylindolo[3,2-b] Carbazole (FICZ) Is a Signaling Molecule in Neurogenesis of Adult Hippocampal Neurons. J Mol Neurosci. 2020; 70: 806–817.
Kimura E, Tohyama C. Embryonic and Postnatal Expression of Aryl Hydrocarbon Receptor mRNA in Mouse Brain. Front Neuroanat. 2017; 11: 4.
Korda MM, Gozhenko AI, Fihura OA, Popovych DV, Żukow X, Popovych IL. Relationships between plasma levels of main adaptogene hormones and EEG&HRV parameters at human with dysadaptation. Journal of Education, Health and Sport. 2021; 11(12): 492-512.
Korda MM, Gozhenko AI, Kuchma IL, Korda IV, Popadynets’OO, Badiuk NS, Korolyshyn TA, Zukow W, Popovych IL. Normal bilirubinemia downregulates the power spectral density of the θ and δ rhythm, instead upregulates the β rhythm and sympatho-vagal balance in adult humans. Journal of Education, Health and Sport. 2022; 12(1): 454-472.
Kotelnikov SA, Nozdrachov AD, Odinak MM, Shustov EB, Kovalenko IYu, Davidenko VYu. Heart rate variability: understanding of the mechanisms [in Russian]. Fiziologiya cheloveka. 2002; 28(1): 130-143.
Kuchma IL, Flyunt I-SS, Ruzhylo SV, Zukow W, Bilas VR, Popovych IL. Varieties of the state of exchange of nitrogenous metabolites (creatinine, urea, uric acid and bilirubin) and their immune accompaniment at rats. Journal of Education, Health and Sport. 2021; 11(7): 228-238.
Kuchma IL, Gozhenko AI, Flyunt ISS, Ruzhylo SV, Kovalchuk GY, Zukow W, Popovych IL. Role of the neuroendocrine complex in immunotropic effects of nitrogenous metabolites in rats. Journal of Education, Health and Sport. 2021; 11(3): 212-230.
Kuchma IL, Gozhenko AI, Ruzhylo SV, Kovalchuk GY, Nahurna YV, Zukow W, Popovych IL. Immunotropic effects of nitrogenous metabolites in healthy humans. Journal of Education, Health and Sport. 2021; 11(5): 197-206.
Kuchma IL, Gozhenko AI, Flyunt I-SS, Ruzhylo SV, Zukow W, Popovych IL. Immunotropic effects of nitrogenous metabolites in patients with chronic pyelonephritis. Journal of Education, Health and Sport. 2021; 11(6): 217-226.
Kuchma IL, Korda MM, Klishch MI, Popovych DV, Żukow X, Popovych IL. Role of autonomous and endocrine factors in immunotropic effects of nitrogenous metabolites in patients with chronic pyelonephritis. Journal of Education, Health and Sport. 2022; 12(5): 362-385.
Li X, Tong Q, Xie D, Chen Z, Pan S, Zhang X, Dong W. Low serum uric acid levels in patients with acute central nervous system viral infections. Neuroreport. 2017; 28(18): 1250-1254.
Montenegro RA, Farinatti P de TV, Fontes EB, Soares PP da S, Cunha da FA, Gurgel JL et al. Transcranial direct current stimulation influences the cardiac autonomic nervous control. Neurosci Lett. 2011; 497(1): 32-36.
Morelli M, Carta AR, Kachroo A, Schwarzschild A. Pathophysiological roles for purines: adenosine, caffeine and urate. Prog Brain Res. 2010; 183: 183-208.
Newberg AB, Alavi A, Baime M, Pourdehnad M, Santanna J, d’Aquili E. The measurement of regional cerebral blood flow during the complex cognitive task of meditation: a preliminary SPECT study. Psychiatry Research: Neuroimaging Section. 2001; 106: 113-122.
Nikolin S, Boonstra TW, Loo CK, Martin D. Combined effect of prefrontal transcranial direct current stimulation and a working memory task on heart rate variability. PLoS One. 2017; 12: e0181833.
Ojo ES, Tischkau SA. The Role of AhR in the Hallmarks of Brain Aging: Friend and Foe. Cells. 2021; 10(10): 2729.
Palma JA, Benarroch EE. Neural control of the heart: recent concepts and clinical correlations. Neurology. 2014; 83: 261-271.
Practical psychodiagnostics. Techniques and tests [in Russian]. Samara. Bakhrakh; 1998: 59-64.
Phelan D, Winter GM, Rogers WJ, Lam JC, Denison MS. Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Arch Biochem Biophys. 1998; 357(1): 155-163.
Piccirillo G, Ottaviani C, Fiorucci C, Petrocci N, Moscucci F, Di Iorio C, et al. Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years. Clin Interv Aging. 2016; 11: 1687-1695.
Popovych IL, Gozhenko AI, Bombushkar IS, Korda MM, Zukow W. Sexual dimorphism in relationships between of uricemia and some psycho-neuro-endocrine parameters. Journal of Education, Health and Sport. 2015; 5(5): 556-581.
Popovych IL, Gozhenko AI, Kuchma IL, Zukow W, Bilas VR, Kovalchuk GY, Ivasivka AS. Immunotropic effects of so-called slag metabolites (creatinine, urea, uric acid and bilirubin) at rats. Journal of Education, Health and Sport. 2020; 10(11): 320-336.
Popovych IL, Kozyavkina OV, Kozyavkina NV, Korolyshyn TA, Lukovych YuS, Barylyak LG. Correlation between Indices of the Heart Rate Variability and Parameters of Ongoing EEG in Patients Suffering from Chronic Renal Pathology. Neurophysiology. 2014; 46(2): 139-148.
Popovych IL, Lukovych YuS, Korolyshyn TA, Barylyak LG, Kovalska LB, Zukow W. Relationship between the parameters heart rate variability and background EEG activity in healthy men. Journal of Health Sciences. 2013; 3(4): 217-240.
Pousti A, Deemyad T, Malihi G. Mechanism of inhibitory effect of citalopram on isolated guinea-pig atria in relation to adenosine receptor. Hum Psychopharmacol. 2004; 19(5): 347-350.
Rebola N, Canas PM, Oliveira CR, Cunha RA. Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat. Neuroscience. 2005; 132: 893–903.
Romodanov AP (editor). Postradiation Encephalopathy. Experimental Researches and Clinical Observations. Kyїv. USRI of Neurosurgery;1993: 224. [in Ukrainian and Russian].
Rosin DL, Robeva A, Woodard RL, Guyenet PG, Linden J. Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system. J Comp Neurol. 1998; 401: 163–186.
Ruzhylo SV, Fihura OA, Zukow W, Popovych IL. Immediate neurotropic effects of Ukrainian phytocomposition. Journal of Education, Health and Sport. 2015; 5(4): 415-427.
Sakaki M, Yoo HJ, Nga L, Lee TH, Thayer JF, Mather M. Heart rate variability is associated with amygdala functional connectivity with MPFC across younger and older adults. Neuroimage. 2016; 139: 44-52.
Shannon CE. A mathematical theory of information. Bell Syst Tech J. 1948; 27: 379-423.
Schiffmann SN, Jacobs O, Vanderhaeghen JJ. Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. J Neurochem. 1991; 57: 1062–1067.
Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health. 2017; 5: 258.
Sofaer JA, Emery AF. Genes for super-intelligence? J Med Genet. 1981; 18: 410-413.
Spielberg JM, Miller GA, Warren SL, Sutton BP, Banich M, Heller W. Transdiagnostic dimensions of anxiety and depression moderate motivation-related brain networks during goal maintenance. Depress Anxiety. 2014; 31(10): 805-813.
Spielberg JM, Schwarz JM, Matyi MA. Anxiety in transition: Neuroendocrine mechanisms supporting the development of anxiety pathology in adolescence and young adulthood. Front Neuroendocrinol. 2019; 55: 100791.
Svenningsson P, Fourreau L, Bloch B, Fredholm BB, Gonon F, Le Moine C. Opposite tonic modulation of dopamine and adenosine on c-fos gene expression in striatopallidal neurons. Neuroscience. 1999; 89: 827–837.
Thayer JF, Lane RD. Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev. 2009; 33(2): 81-88.
Taylor JA, Carr DL, Myers CW, Eckberg DL. Mechanisms underlying very-low-frequency RR-interval oscillations in humans. Circulation. 1998; 98(6): 547-555.
Theorell T, Liljeholm-Johansson Y, Björk H, Ericson M. Saliva testosterone and heart rate variability in the professional symphony orchestra after "public faintings" of an orchestra member. Psychoneuroendocrinology. 2007; 32(6): 660-668.
Verberne AJ. Medullary sympathoexcitatory neurons are inhibited by activation of the medial prefrontal cortex in the rat. Am J Physiol. 1996; 270(4Pt2): R713-R719.
Verberne AJ, Lam W, Owens NC, Sartor D. Supramedullary modulation of sympathetic vasomotor function. Clin Exp Pharmacol Physiol. 1997;24(9-10):748-754.
Vink JJT, Mandija S, Petrov PI, van den Berg CAT, Sommer IEC, Neggers SFW. A novel concurrent TMS-fMRI method to reveal propagation patterns of prefrontal magnetic brain stimulation. Hum Brain Mapp. 2018; 39(11): 4580-4592.
Wang X, Hawkins BT, Miller DS. Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. FASEB J. 2011; 25: 644–652.
Winkelmann T, Thayer JF, Pohlack S, Nees F, Grimm O, Flor H. Structural brain correlates of heart rate variability in a healthy young adult population. Brain Struct Funct. 2017; 222(2): 1061-1068.
Yoo HJ, Thayer JF, Greening S, Lee TH, Ponzio A, Min J, Sakaki M, Nga L, Mather M, Koenig J. Brain structural concomitants of resting state heart rate variability in the young and old: evidence from two independent samples. Brain Struct Funct. 2018; 223(2): 727-737.
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