CC..png    

Legal and postal addresses of the publisher: office 1336, 17 Naberezhnaya Severnoy Dviny, Arkhangelsk, 163002, Russian Federation, Northern (Arctic) Federal University named after M.V. Lomonosov

Phone: (818-2) 21-61-21
E-mail: vestnik_med@narfu.ru
https://vestnikmed.ru/en/

ABOUT JOURNAL

The Role of the Acetylcholine System and Its Components in the Development of Post-COVID Syndromes (Review). 240-252

Версия для печати

Section: Review articles

UDC

[612.8.04+612.81]:[616-008.64+616-009]

DOI

10.37482/2687-1491-Z182

Authors

Sergey P. Lysenkov* ORCID: https://orcid.org/0000-0003-1179-8938
Dmitriy V. Muzhenya* ORCID: https://orcid.org/0000-0002-4379-0634

*Maykop State Technological University
(Maykop, Russia)

Corresponding author: Dmitriy Muzhenya, address: ul. Pervomaiskaya 191, Maykop, 385000, Russia; e-mail: dmuzhenya@mail.ru

Abstract

According to the latest data, COVID-19 is classified as a respiratory virus. However, it has been proven to cause a significant multi-organ dysfunction. Despite the increase in the effectiveness of treatment tactics, a post-COVID-19 symptom complex has been observed in patients after recovery, manifesting itself as cephalalgia, brain fog, high fever, muscle weakness and a decrease (or increase) in arterial pressure. To describe this condition, a clinical characteristic has been proposed: post-acute COVID-19 syndrome (PACS). Approximately 57 % of patients hospitalized with COVID-19 have symptoms of PACS even one year after initial infection with COVID-19. This pathological condition is being actively studied, but the question of the causes of PACS and its development mechanisms remains open. One of the possible reasons behind this symptomatology, in our opinion, is a disorder of the body’s acetylcholine system and its components. The acetylcholine system plays an integral role in various physiological and pathophysiological processes, such as the regulation of the muscular system, immune and inflammatory reactions, wound healing, as well as the development of cardiovascular, respiratory and other diseases. A key way of translating acetylcholine signals in the body is through the use of neurotransmission via a chemical synapse. Based on current literature data, there is reason to believe that viral invasion can significantly change the functional activity of the vagus nerve by disrupting signal transmission in a synapse. We believe that the hyperimmune response caused by COVID-19 triggers a chain of pathological mechanisms that are associated with disrupted nitric oxide production and imbalance in acetylcholine and its receptors. An understanding of these processes may open up prospects for improving the effectiveness of treatment and rehabilitation of patients with COVID-19.

Keywords

acetylcholine system disorder, neuromuscular junction, synaptic signalling disorder, consequences of COVID-19, post-COVID syndrome
Download (pdf, 0.3MB )

References

  1. WHO COVID-19 Dashboard. Available at: https://covid19.who.int/ (accessed: 4 April 2023).
  2. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li X., Liu M., Xiao Y., Gao H., Guo L., Xie J., Wang G., Jiang R., Gao H., Jin Q., Wang J., Cao B. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. Lancet, 2020, vol. 395, no. 10223, pp. 497–506. https://doi.org/10.1016/s0140-6736(20)30183-5
  3. Yahia A.I.O. Liver Injury and Dysfunction Associated with COVID-19: A Review Article. Clin. Lab., 2022, vol. 68, no. 1. https://doi.org/10.7754/clin.lab.2021.210535
  4. Ayoubkhani D., Khunti K., Nafilyan V., Maddox T., Humberstone B., Diamond I., Banerjee A. Post-Covid Syndrome in Individuals Admitted to Hospital with Covid-19: Retrospective Cohort Study. BMJ, 2021, vol. 372. Art. no. n693. https://doi.org/10.1136/bmj.n693
  5. Desai A.D., Lavelle M., Boursiquot B.C., Wan E.Y. Long-Term Complications of COVID-19. Am. J. Physiol. Cell Physiol., 2022, vol. 322, no. 1, pp. C1–C11. https://doi.org/10.1152/ajpcell.00375.2021
  6. Tobler D.L., Pruzansky A.J., Naderi S., Ambrosy A.P., Slade J.J. Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician. Curr. Atheroscler. Rep., 2022, vol. 24, no. 7, pp. 563–570. https://doi.org/10.1007/s11883-022-01032-8
  7. Willi S., Lüthold R., Hunt A., Hänggi N.V., Sejdiu D., Scaff C., Bender N., Staub K., Schlagenhauf P. COVID-19 Sequelae in Adults Aged Less Than 50 Years: A Systematic Review. Travel Med. Infect. Dis., 2021, vol. 40. Art. no. 101995. https://doi.org/10.1016/j.tmaid.2021.101995
  8. Haam J., Yakel J.L. Cholinergic Modulation of the Hippocampal Region and Memory Function. J. Neurochem., 2017, vol. 142, suppl. 2, pp. 111–121. https://doi.org/10.1111/jnc.14052
  9. Mesulam M. The Cholinergic Lesion of Alzheimer’s Disease: Pivotal Factor or Side Show? Learn. Mem., 2004, vol. 11, no. 1, pp. 43–49. https://doi.org/10.1101/lm.69204
  10. Picciotto M.R., Higley M.J., Mineur Y.S. Acetylcholine as а Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior. Neuron, 2012, vol. 76, no. 1, pp. 116–129. https://doi.org/10.1016/j.neuron.2012.08.036
  11. Ahmed N.Y., Knowles R., Dehorter N. New Insights into Cholinergic Neuron Diversity. Front. Mol. Neurosci., 2019, no. 12. Art. no. 204. https://doi.org/10.3389/fnmol.2019.00204
  12. Rima M., Lattouf Y., Younes M.A., Bullier E., Legendre P., Mangin J.-M., Hong E. Dynamic Regulation of the Cholinergic System in the Spinal Central Nervous System. Sci. Rep., 2020, vol. 10. Art. no. 15338. https://doi.org/10.1038/s41598-020-72524-3
  13. Bosmans G., Shimizu Bassi G., Florens M., Gonzalez-Dominguez E., Matteoli G., Boeckxstaens G.E. Cholinergic Modulation of Type 2 Immune Responses. Front. Immunol., 2017, vol. 8. Art. no. 1873. https://doi.org/10.3389/fimmu.2017.01873
  14. Scott G.D., Fryer A.D. Role of Parasympathetic Nerves and Muscarinic Receptors in Allergy and Asthma. Chem. Immunol. Allergy, 2012, no. 98, pp. 48–69. https://doi.org/10.1159/000336498
  15. Saw E.L., Pearson J.T., Schwenke D.O., Munasinghe P.E., Tsuchimochi H., Rawal S., Coffey S., Davis P., Bunton R., Van Hout I., Kai Y., Williams M.J.A., Kakinuma Y., Fronius M., Katare R. Activation of the Cardiac Non-Neuronal Cholinergic System Prevents the Development of Diabetes-Associated Cardiovascular Complications. Cardiovasc. Diabetol., 2021, vol. 20, no. 1. Art. no. 50. https://doi.org/10.1186/s12933-021-01231-8
  16. Eccles J.C., Fatt P., Koketsu K. Cholinergic and Inhibitory Synapses in a Pathway from Motor-Axon Collaterals to Motoneurones. J. Physiol., 1954, vol. 126, no. 3, pp. 524–562. https://doi.org/10.1113/jphysiol.1954.sp005226
  17. Chen J., Mizushige T., Nishimune H. Active Zone Density Is Conserved During Synaptic Growth but Impaired in Aged Mice. J. Comp. Neurol., 2012, vol. 520, no. 2, pp. 434–452. https://doi.org/10.1002/cne.22764
  18. Schiavo G., Stenbeck G., Rothman J.E., Söllner T.H. Binding of the Synaptic Vesicle v-SNARE, Synaptotagmin, to the Plasma Membrane t-SNARE, SNAP-25, Can Explain Docked Vesicles at Neurotoxin-Treated Synapses. Proc. Natl. Acad. Sci. USA, 1997, vol. 94, no. 3, pp. 997–1001. https://doi.org/10.1073/pnas.94.3.997
  19. White D.N., Stowell M.H.B. Room for Two: The Synaptophysin/Synaptobrevin Complex. Front. Synaptic Neurosci., 2021, vol. 13. Art. no. 740318. https://doi.org/10.3389/fnsyn.2021.740318
  20. Krause M., Wernig A. The Distribution of Acetylcholine Receptors in the Normal and Denervated Neuromuscular Junction of the Frog. J. Neurocytol., 1985, vol. 14, no. 5, pp. 765–780. https://doi.org/10.1007/BF01170827
  21. Fujita A., Cheng J., Tauchi-Sato K., Takenawa T., Fujimoto T. A Distinct Pool of Phosphatidylinositol 4,5-Bisphosphate in Caveolae Revealed by a Nanoscale Labeling Technique. Proc. Natl. Acad. Sci. USA, 2009, vol. 106, no. 23, pp. 9256–9261. https://doi.org/10.1073/pnas.0900216106
  22. Petrov A.M., Zefirov A.L. Kholesterin i lipidnye plotiki biologicheskikh membran. Rol’ v sekretsii, retseptsii i funktsionirovanii ionnykh kanalov [Cholesterol and Lipid Rafts in the Biological Membranes. Role in the Release, Reception and Ion Channel Functions]. Uspekhi fiziologicheskikh nauk, 2013, vol. 44, no. 1, pp. 17–38.
  23. Gazzerro E., Sotgia F., Bruno C., Lisanti M.P., Minetti C. Caveolinopathies: From the Biology of Caveolin-3 to Human Diseases. Eur. J. Hum. Genet., 2010, vol. 18, no. 2, pp. 137–145. https://doi.org/10.1038/ejhg.2009.103
  24. Hausser A., Schlett K. Coordination of AMPA Receptor Trafficking by Rab GTPases. Small GTPases, 2019, vol. 10, no. 6, pp. 419–432. https://doi.org/10.1080/21541248.2017.1337546
  25. Zakany F., Kovacs T., Panyi G., Varga Z. Direct and Indirect Cholesterol Effects on Membrane Proteins with Special Focus on Potassium Channels. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2020, vol. 1865, no. 8. Art. no. 158706. https://doi.org/10.1016/j.bbalip.2020.158706
  26. Kravtsova V.V., Matchkov V.V., Bouzinova E.V., Vasiliev A.N., Razgovorova I.A., Heiny J.A., Krivoi I.I. Isoform-Specific Na,K-ATPase Alterations Precede Disuse-Induced Atrophy of Rat Soleus Muscle. Biomed. Res. Int., 2015, vol. 2015. Art. no. 720172. https://doi.org/10.1155/2015/720172
  27. McHardy S.F., Wang H.L., McCowen S.V., Valdez M.C. Recent Advances in Acetylcholinesterase Inhibitors and Reactivators: An Update on the Patent Literature (2012–2015). Expert Opin. Ther. Pat., 2017, vol. 27, no. 4, pp. 455–476. https://doi.org/10.1080/13543776.2017.1272571
  28. Bonaz B., Sinniger V., Pellissier S. Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases. Front. Neurosci., 2021, vol. 15. Art. no. 650971. https://doi.org/10.3389/fnins.2021.650971
  29. de Jonge W.J., Ulloa L. The Alpha7 Nicotinic Acetylcholine Receptor as a Pharmacological Target for Inflammation. Br. J. Pharmacol., 2007, vol. 151, no. 7, pp. 915–929. https://doi.org/10.1038/sj.bjp.0707264
  30. Brenner H.R., Akaaboune M. Recycling of Acetylcholine Receptors at Ectopic Postsynaptic Clusters Induced by Exogenous Agrin in Living Rats. Dev. Biol., 2014, vol. 394, no. 1, pp. 122–128. https://doi.org/10.1016/j.ydbio.2014.07.018
  31. Barrantes F.J. Cell-Surface Translational Dynamics of Nicotinic Acetylcholine Receptors. Front. Synaptic Neurosci., 2014, vol. 6. Art. no. 25. https://doi.org/10.3389/fnsyn.2014.00025
  32. Karimi N., Okhovat A.A., Ziaadini B., Haghi Ashtiani B., Nafissi S., Fatehi F. Myasthenia Gravis Associated with Novel Coronavirus 2019 Infection: A Report of Three Cases. Clin. Neurol. Neurosurg., 2021, vol. 208. Art. no. 106834. https://doi.org/10.1016/j.clineuro.2021.106834
  33. Alexandris N., Lagoumintzis G., Chasapis C.T., Leonidas D.D., Papadopoulos G.E., Tzartos S.J., Tsatsakis A., Eliopoulos E., Poulas K., Farsalinos K. Nicotinic Cholinergic System and COVID-19: In silico Evaluation of Nicotinic Acetylcholine Receptor Agonists as Potential Therapeutic Interventions. Toxicol. Rep., 2020, vol. 8, pp. 73–83. https://doi.org/10.1016/j.toxrep.2020.12.013
  34. Bruneau E.G., Akaaboune M. The Dynamics of Recycled Acetylcholine Receptors at the Neuromuscular Junction in vivo. Development, 2006, vol. 133, no. 22, pp. 4485–4493. https://doi.org/10.1242/dev.02619
  35. Lück G., Hoch W., Hopf C., Blottner D. Nitric Oxide Synthase (NOS-1) Coclustered with Agrin-Induced AChR-Specializations on Cultured Skeletal Myotubes. Mol. Cell. Neurosci., 2000, vol. 16, no. 3, pp. 269–281. https://doi.org/10.1006/mcne.2000.0873
  36. Klyachko V.A., Ahern G.P., Jackson M.B. cGMP-Mediated Facilitation in Nerve Terminals by Enhancement of the Spike Afterhyperpolarization. Neuron, 2001, vol. 31, no. 6, pp. 1015–1025. https://doi.org/10.1016/s0896-6273(01)00449-4
  37. Sayed N., Baskaran P., Ma X., van den Akker F., Beuve A. Desensitization of Soluble Guanylyl Cyclase, the NO Receptor, by S-Nitrosylation. Proc. Natl. Acad. Sci. USA, 2007, vol. 104, no. 30, pp. 12312–12317. https://doi.org/10.1073/pnas.0703944104
  38. Proskurina S.E. Vliyanie oksida azota (NO) na aktivnost’ fermenta atsetilkholinesterazy v nervno-myshechnom sinapse krysy [Effect of Nitric Oxide (NO) on the Activity of the Acetylcholinesterase Enzyme in Rat Neuromuscular Junction: Diss.]. Kazan, 2016. 134 p.
  39. Petrov K.A., Malomouzh A.I., Kovyazina I.V., Krejci E., Nikitashina A.D., Proskurina S.E., Zobov V.V., Nikolsky E.E. Regulation of Acetylcholinesterase Activity by Nitric Oxide in Rat Neuromuscular Junction via N-Methyl- D-Aspartate Receptor Activation. Eur. J. Neurosci., 2013, vol. 37, no. 2, pp. 181–189. https://doi.org/10.1111/ejn.12029
  40. Rosas-Ballina M., Ochani M., Parrish W.R., Ochani K., Harris Y.T., Huston J.M., Chavan S., Tracey K.J. Splenic Nerve Is Required for Cholinergic Antiinflammatory Pathway Control of TNF in Endotoxemia. Proc. Natl. Acad. Sci. USA, 2008, vol. 105, no. 31, pp. 11008–11013. https://doi.org/10.1073/pnas.0803237105
  41. Balez R., Ooi L. Getting to NO Alzheimer’s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide. Oxid. Med. Cell. Longev., 2016, vol. 2016. Art. no. 3806157. https://doi.org/10.1155/2016/3806157
  42. Gilhus N.E., Tzartos S., Evoli A., Palace J., Burns T.M., Verschuuren J.J.G.M. Myasthenia Gravis. Nat. Rev. Dis. Primers, 2019, vol. 5, no. 1. Art. no. 30. https://doi.org/10.1038/s41572-019-0079-y
  43. Leoni V., Caccia C. The Impairment of Cholesterol Metabolism in Huntington Disease. Biochim. Biophys. Acta, 2015, vol. 1851, no. 8, pp. 1095–1105. https://doi.org/10.1016/j.bbalip.2014.12.018
  44. Grajales-Reyes G.E., Báez-Pagán C.A., Zhu H., Grajales-Reyes J.G., Delgado-Vélez M., García-Beltrán W.F., Luciano C.A., Quesada O., Ramírez R., Gómez C.M., Lasalde-Dominicci J.A. Transgenic Mouse Model Reveals an Unsuspected Role of the Acetylcholine Receptor in Statin-Induced Neuromuscular Adverse Drug Reactions. Pharmacogenomics J., 2013, vol. 13, no. 4, pp. 362–368. https://doi.org/10.1038/tpj.2012.21
  45. Crespi B., Alcock J. Conflicts Over Calcium and the Treatment of COVID-19. Evol. Med. Public Health, 2021, vol. 9, no. 1, pp. 149–156. https://doi.org/10.1093/emph/eoaa046
  46. Ramadan J.W., Steiner S.R., O’Neill C.M., Nunemaker C.S. The Central Role of Calcium in the Effects of Cytokines on Beta-Cell Function: Implications for Type 1 and Type 2 Diabetes. Cell Calcium, 2011, vol. 50, no. 6, pp. 481–490. https://doi.org/10.1016/j.ceca.2011.08.005
  47. Luciani D.S., Gwiazda K.S., Yang T.L., Kalynyak T.B., Bychkivska Y., Frey M.H., Jeffrey K.D., Sampaio A.V., Underhill T.M., Johnson J.D. Roles of IP3R and RyR Ca2+ Channels in Endoplasmic Reticulum Stress and β-Cell Death. Diabetes, 2009, vol. 58, no. 2, pp. 422–432. https://doi.org/10.2337/db07-1762
  48. Berchtold M.W., Brinkmeier H., Müntener M. Calcium Ion in Skeletal Muscle: Its Crucial Role for Muscle Function, Plasticity, and Disease. Physiol. Rev., 2000, vol. 80, no. 3, pp. 1215–1265. https://doi.org/10.1152/physrev.2000.80.3.1215
  49. Guo T., Fan Y., Chen M., Wu X., Zhang L., He T., Wang H., Wan J., Wang X., Lu Z. Cardiovascular Implications of Fatal Outcomes of Patients with Coronavirus Disease 2019 (COVID-19). JAMA Cardiol., 2020, vol. 5, no. 7, pp. 811–818. https://doi.org/10.1001/jamacardio.2020.1017
  50. Arentz M., Yim E., Klaff L., Lokhandwala S., Riedo F.X., Chong M., Lee M. Characteristics and Outcomes of 21 Critically Ill Patients with COVID-19 in Washington State. JAMA, 2020, vol. 323, no. 16, pp. 1612–1614. https://doi.org/10.1001/jama.2020.4326
  51. Dani M., Dirksen A., Taraborrelli P., Torocastro M., Panagopoulos D., Sutton R., Lim P.B. Autonomic Dysfunction in ‘Long COVID’: Rationale, Physiology and Management Strategies. Clin. Med. (Lond.), 2021, vol. 21, no. 1, pp. e63–e67. https://doi.org/10.7861/clinmed.2020-0896
  52. Jung F., Krüger-Genge A., Franke R.P., Hufert F., Küpper J.H. COVID-19 and the Endothelium. Clin. Hemorheol. Microcirc., 2020, vol. 75, no. 1, pp. 7–11. https://doi.org/10.3233/ch-209007
  53. Jardine D.L., Wieling W., Brignole M., Lenders J.W.M., Sutton R., Stewart J. The Pathophysiology of the Vasovagal Response. Heart Rhythm, 2018, vol. 15, no. 6, pp. 921–929. https://doi.org/10.1016/j.hrthm.2017.12.013
  54. Chung S.A., Yuan H., Chung F. A Systemic Review of Obstructive Sleep Apnea and Its Implications for Anesthesiologists. Anesth. Analg., 2008, vol. 107, no. 5, pp. 1543–1563. https://doi.org/10.1213/ane.0b013e318187c83a
  55. Monahan K.D. Effect of Aging on Baroreflex Function in Humans. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2007, vol. 293, no. 1, pp. R3–R12. https://doi.org/10.1152/ajpregu.00031.2007



Make a Submission


INDEXED IN: 

DOAJ_logo-colour.png

Elibrary.ru

logotype.png

infobaseindex

Логотип.png




Лань

OTHER NArFU JOURNALS: 

Vestnik of NArFU.
Series "Humanitarian and Social Sciences"

Forest Journal 
Лесной журнал 

Arctic and North