Normal bilirubinemia downregulates the power spectral density of the θ and Δ rhythm, instead upregulates the β rhythm and sympatho-vagal balance in adults humans
DOI:
https://doi.org/10.12775/JEHS.2022.12.01.039Keywords
bilirubinemia, EEG, HRV, relationships, adults humansAbstract
Background. Neonatal hyperbilirubinemia has been known to damage neural function. Our goal is to determine whether the neurotropic activity of normal bilirubinemia in adults is evident. Methods. The object of observation were 77 volunteers: 30 women and 47 men aged 49±13 (26 ÷ 76) years without clinical diagnosis. Testing was performed twice with an interval of 4 ÷ 10 days. We determined the plasma levels of the direct and free bilirubin, recorded EEG and HRV followed by analysis of correlations between parameters. Results. Significant downregulating effect of bilirubinemia was found on power spectrum density (PSD) theta and delta rhythm. In contrast, bilirubinemia has an upregulating effect on PSD beta rhythm and sympatho-vagal balance. The canonical correlation between direct & free bilirubin levels, on the one hand, and EEG & HRV parameters, on the other hand, is very strong: R=0,808; R2=0,654; χ2(80)=191; p<10-6 (n=154). A similar canonical correlation was found between individual changes in parameters: R=0,753; R2=0,568; χ2(48)=83; p=0,001 (n=74). Conclusion. Even normal bilirubinemia has an downregulating effect on mainly theta and delta rhythm-generating nuclei and vagal tone, while upregulating effects on sympathetic tone and beta rhythm-generating nuclei.
References
Shapiro SM, Conlee JW. Brainstem auditory evoked potentials correlate with morphological changes in Gunn rat pups. Hear Res. 1991;57:16-22.
Watchko JF, Kernicterus and the molecular mechanisms of bilirubin-induced CNS injury in newborns. Neuromolecular Med. 2006;8:513-529.
Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Engl J Med. 2001;344:581-590.
Watchko JF, Tiribelli C. Bilirubin-induced neurologic damage - Mechanisms and management approaches. N Engl J Med. 2013;369:2021-2030.
Chang FY, Lee CC, Huang CC, Hsu KS. Unconjugated bilirubin exposure impairs hippocampal long-term synaptic plasticity. PLoS One. 2009;4(6):e5876. doi:10.1371/journal.pone.0005876
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. doi:10.1159/000494101
Dani C, Pratesi S, Mannaioni G, Gerace E. Neurotoxicity of Unconjugated Bilirubin in Neonatal Hypoxic-Ischemic Brain Injury in vitro. Front Pediatr. 2021;9:659477. doi:10.3389/fped.2021.659477
Liang M, Yin X-L, Shi H-B, Li C-Y, Li X-Y, Song N-Y, Shi H-S, Zhao Y, Wang L-Y, Yin S-K. Bilirubin augments Ca2+ load of developing bushy neurons by targeting specific subtype of voltage-gated calcium channels. Sci Rep. 2017;7:431.
Han G-Y, Li C-Y, Shi H-B, Wang J-P, Su K-M, Yin X-L, Yin S-K. Riluzole is a promising pharmacological inhibitor of bilirubin-induced excitotoxicity in the ventral cochlear nucleus. CNS Neurosci Ther. 2015;21:262-270.
Chai S, Li M, Lan J, Xiong Z-G, Saugstad JA, Simon R. P. A kinase-anchoring protein 150 and calcineurin are involved in regulation of acid-sensing ion channels ASIC1a and ASIC2a. J Biol Chem. 2007;282:22668-22677.
Allen NJ, Attwell D. Modulation of ASIC channels in rat cerebellar Purkinje neurons by ischaemia-related signals. J Physiol. 2002;543:521-529.
Lai K, Song X-L, Shi H-S, Qi X, Li Ch-Y, Fang J, Wang F, Maximyuk O, Krishtal O, et al. Bilirubin enhances the activity of ASIC channels to exacerbate neurotoxicity in neonatal hyperbilirubinemia in mice. Sci Transl Med. 2020;12(530):eaax1337.
Goryachkovskiy АМ. Clinical Biochemistry. Odesa: Astroprint; 1998: 608. [in Russian].
Heart Rate Variability. Standards of Measurement, Physiological Interpretation, and Clinical Use. Task Force of ESC and NASPE. Circulation. 1996;93(5):1043-1065.
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.
Baevskiy RM, Ivanov GG. Heart Rate Variability: theoretical aspects and possibilities of clinical application. Ultrazvukovaya i funktsionalnaya diagnostika. 2001;3:106-127. [in Russian].
Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health. 2017;5:258. doi:10.3389/fpubh.2017.00258
Kul’chyns’kyi AB, Kyjenko VM, Zukow W, Popovych IL. Causal neuro-immune relationships at patients with chronic pyelonephritis and cholecystitis. Correlations between parameters EEG, HRV and white blood cell count. Open Medicine. 2017;12(1):201-213.
Popadynets’ O, Gozhenko A, Badyuk N, Popovych I, Skaliy A, Hagner-Derengowska M, Napierata M, Muszkieta R, Sokołowski D, Zukow W, Rybałko L. Interpersonal differences caused by adaptogen changes in entropies of EEG, HRV, immunocytogram, and leukocytogram. JPES. 2020;20(Suppl 2):982-999.
Gozhenko АІ, Korda MM, Popadynets’ OO, Popovych IL. Entropy, Harmony, Synchronization and their Neuro-endocrine-immune Correlates. Odesa. Feniks; 2021: 232. [in Ukrainian].
Buzsaki G. Theta oscillations in the hippocampus. Neuron. 2002;33:325–340.
Romodanov AP (editor). Postradiation Encephalopathy. Experimental Researches and Clinical Observations. Kyiv:USRI of Neurosurgery;1993:224. [in Ukrainian and Russian].
Benarroch EE. The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc. 1993;68(10):988-1001. doi:10.1016/s0025-6196(12)62272-1
Palma JA, Benarroch EE. Neural control of the heart: recent concepts and clinical correlations. Neurology. 2014;83:261-271. doi: 10.1212/WNL.0000000000000605
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. doi:10.1016/j.neubiorev.2008.08.004
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. doi:10.1152/ajpregu.1996.270.4.R713
Verberne AJ, Lam W, Owens NC, Sartor D. Supramedullary modulation of sympathetic vasomotor function. Clin Exp Pharmacol Physiol. 1997;24(9-10):748-754. doi:10.1111/j.1440-1681.1997.tb02126.x
Gianaros PJ. Brain-body pathways to cardiovascular disease risk. In: Herbert Weiner Early Career Award Lecture, 66th Annual Meeting of the American Psychosomatic Society, Baltimore, MD, March 2008.
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. doi:10.1016/j.neuroimage.2016.05.076
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. doi:10.1016/j.brs.2017.05.002
Remue J, Vanderhasselt MA, Baeken C, Rossi V, Tullo J, De Raedt R. The effect of a single HF-rTMS session over the left DLPFC on the physiological stress response as measured by heart rate variability. Neuropsychology. 2016;30(6):756-766. doi:10.1037/neu0000255
Guo, CC, Sturm V E, 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. doi: 10.1073/pnas.1509184113
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. doi:10.1007/s00429-016-1185-1
Thayer JF, Ǻhs F, Fredrikson M, Sollers JJ 3rd, Wager TD. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci Biobehav Rev. 2012;36(2):747-756. doi:10.1016/j.neubiorev.2011.11.009
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. doi:10.1007/s00429-017-1519-7
Carnevali L, Koenig J, Sgoifo A, Ottaviani C. Autonomic and Brain Morphological Predictors of Stress Resilience. Front Neurosci. 2018;12:228.
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. doi:10.1002/hbm.24307
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. doi:10.1080/10253890.2019.1625884
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.
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. doi:10.1016/j.neulet.2011.04.019
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. doi:10.2147/CIA.S116194
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.
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. doi:10.1016/j.brs.2019.10.006
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.
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.
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.
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. doi:10.1006/abbi.1998.0814
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. doi:10.1038/srep19618.
Ojo ES, Tischkau SA. The Role of AhR in the Hallmarks of Brain Aging: Friend and Foe. Cells. 2021;10(10):2729. doi:10.3390/cells10102729
Kimura E, Tohyama C. Embryonic and Postnatal Expression of Aryl Hydrocarbon Receptor mRNA in Mouse Brain. Front Neuroanat. 2017;11:4. doi:10.3389/fnana.2017.00004.
Latchney SE, Hein AM, O’Banion MK, DiCicco-Bloom E, Opanashuk LA. Deletion or activation of the aryl hydrocarbon receptor alters adult hippocampal neurogenesis and contextual fear memory. J Neurochem. 2013;125:430-445. doi:10.1111/jnc.12130.
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. doi:10.1096/fj.10-169227.
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. doi:10.1186/s12974-019-1572-7.
Yu AR, Jeong YJ, Hwang CY, Yoon KS, Choe W, Ha J, Kim SS, Pak YK, Yeo EJ, Kang I. Alpha-naphthoflavone induces apoptosis through endoplasmic reticulum stress via c-Src-, ROS-, MAPKs-, and arylhydrocarbon receptor-dependent pathways in HT22 hippocampal neuronal cells. Neurotoxicology. 2019;71:39–51. doi:10.1016/j.neuro.2018.11.011.
Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, Chao CC, Patel B, Yan R, Blain M, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016;22:586–597. doi:10.1038/nm.4106.
Rothhammer V, Borucki DM, Tjon EC, Takenaka MC, Chao CC, Ardura-Fabregat A, de Lima KA, Gutierrez-Vazquez C, Hewson P, Staszewski O, et al. Microglial control of astrocytes in response to microbial metabolites. Nature. 2018;557:724–728. doi:10.1038/s41586-018-0119-x.
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. doi:10.1016/j.jes.2017.07.010.
De la Parra J, Cuartero MI, Perez-Ruiz A, Garcia-Culebras A, Martin R, Sanchez-Prieto J, Garcia-Segura JM, Lizasoain I, Moro MA. AhR Deletion Promotes Aberrant Morphogenesis and Synaptic Activity of Adult-Generated Granule Neurons and Impairs Hippocampus-Dependent Memory. eNeuro. 2018;5 doi:10.1523/ENEURO.0370-17.2018.
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. doi:10.1007/s12031-020-01506-x.
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. doi:10.1038/nn.4222.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Mykhaylo Korda, Anatoliy Gozhenko, Igor Kuchma, Inna Korda, Oleksandr Popadynets’, Nataliya Badiuk, Tetyana Korolyshyn, Walery Zukow, Igor Popovych
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 186
Number of citations: 0
