The myoprotective effect of non-quantal acetylcholine: in vitro model of the myopathy component of chronic inflammatory demyelinating polyneuropathy
- Authors: Gavrichenko A.V.1,2, Pasatetckaia N.A.1,3, Sokolova M.G.4, Lopatina E.V.1,2
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Affiliations:
- First Saint Petersburg State Medical University
- Pavlov Institute of Physiology
- Almazov National Medical Research Centre
- Herzen State Pedagogical University of Russia
- Issue: Vol 16, No 3 (2022)
- Pages: 41-46
- Section: Original articles
- URL: https://ogarev-online.ru/2075-5473/article/view/124053
- DOI: https://doi.org/10.54101/ACEN.2022.3.5
- ID: 124053
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Abstract
Introduction. Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the most common primary polyneuropathies. A degenerative process is the underlying cause of muscular atrophy in CIDP, while muscle strength may not fully recover in patients after pathogenesis-based treatment, thus extending the period of disability. Information about factors affecting the trophic function of muscles can be used to treat neuromuscular disorders.
Study aim — to examine the trophotropic properties of the study participants' blood plasma and the myoprotective effect of acetylcholine concentration equivalent to non-quantal release, using an in vitro model of the myopathy component of CIDP.
Materials and methods. The study included 25 patients diagnosed with typical CIDP in accordance with the EFNS/PNS 2010 criteria. The control group consisted of 25 healthy individuals. Serum antibody levels to the nicotinic acetylcholine receptor were measured in all study participants. A method for organotypic cultivation of skeletal muscle tissue and an in vitro model of the myopathy component of CIPD were developed. The effect of the study participants' blood plasma on the growth of skeletal muscle explants in organotypic culture was assessed.
Results. Patients with CIPD were found to have symmetrical sensorimotor polyneuropathy of varying severity (100%); muscle atrophy (88%), and sensory ataxia (84%). The median INCAT Overall Disability Sum Score was 2 [1; 3] for the arms and 3 [2; 5] for the legs. The median Neurological Impairment Scale (NIS) score was 17 [10; 34]. The nicotinic acetylcholine receptor antibody levels were higher in patients with CIDP (0.47 [0.31; 0.54] nmol/l) than in the control group (0.02 [0.01; 0.03] nmol/l). For the first time, a myotoxic effect of the blood plasma from patients with CIDP was observed in organotypic skeletal muscle culture. Using 1:70 and 1:100 dilutions, patient blood plasma inhibited the growth of explants by 27% (n = 120; p < 0.001) and 21% (n = 120; p < 0.001), respectively. This myotoxic effect removed acetylcholine at a concentration equivalent to non-quantal release (10–8 М).
Conclusion. These results expand our understanding of skeletal muscle damage in CIPD and the role of non-quantal acetylcholine in regulating skeletal muscle growth.
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##article.viewOnOriginalSite##About the authors
Arthur V. Gavrichenko
First Saint Petersburg State Medical University; Pavlov Institute of Physiology
Author for correspondence.
Email: arthyrgavrichenko@gmail.com
ORCID iD: 0000-0002-1286-7192
neurologist
Russian Federation, St. Petersburg; St. PetersburgNatalia A. Pasatetckaia
First Saint Petersburg State Medical University; Almazov National Medical Research Centre
Email: 79046449523@yandex.ru
ORCID iD: 0000-0001-8979-6460
Cand. Sci. (Biol.), Associate Professor, Department of normal physiology, junior researcher
Russian Federation, St. Petersburg; St. PetersburgMaria G. Sokolova
Herzen State Pedagogical University of Russia
Email: sokolova.m08@mail.ru
ORCID iD: 0000-0002-3829-9971
D. Sci. (Med.), Associate Professor, Department of human and animal anatomy and physiology
Russian Federation, St. PetersburgEkaterina V. Lopatina
First Saint Petersburg State Medical University; Pavlov Institute of Physiology
Email: evlopatina@yandex.ru
ORCID iD: 0000-0003-0729-5852
D. Sci. (Biol.), Head, Department of normal physiology, leading researcher, Laboratory of physiology of cardiovascular system and lymphology
Russian Federation, St. Petersburg; St. PetersburgReferences
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