Gap junction protein connexin 43 and its distribution in damaged nerve cells

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Abstract

BACKGROUND: Connexins, particularly connexin 43, form gap junctions that mediate neuron-glial communication. To date, the expression of connexin 43 in phenotypically distinct neurolemmocytes, in particular non-myelinating (Remak cells) and repair Schwann cells, has not been studied.

AIM: To determine the presence of connexin 43 in Schwann cells of the rat sciatic nerve under normal conditions and after mechanical damage by applying a ligature.

MATERIALS AND METHODS: The study was carried out on Wistar rats (n = 10). In experimental rats, the sciatic nerve was damaged by applying a ligature (40 s). 7 days after surgery, sciatic nerve segments were isolated for subsequent immunohistochemical study using antibodies to connexin 43 and glial fibrillary acidic protein (GFAP). In the control group rats, segments of intact sciatic nerves were isolated in a similar way.

RESULTS: It has been shown that in the endoneurium of the intact rat sciatic nerve there are no cells expressing connexin 43. It was found that 7 days after injury, a large number of connexin-43-immunopositive cells of irregular shape with several processes were identified in the endoneurium of the damaged nerve. There was a lack of expression of connexin 43 in GFAP-containing Schwann cells.

CONCLUSIONS: It can be stated that nerve damage leads to active synthesis of the studied protein by endoneurium cells; however, the origin of the cells expressing connexin 43 remains to be elucidated.

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About the authors

Elena A. Kolos

Institute of Experimental Medicine

Email: koloselena1984@yandex.ru
ORCID iD: 0000-0002-9643-6831
SPIN-code: 1479-5992
Scopus Author ID: 55354374400
ResearcherId: D-1579-2012

Research Associate, Laboratory of Functional Morphology of the Central and Peripheral Nervous System, Department of General and Special Morphology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Dmitrii E. Korzhevskii

Institute of Experimental Medicine

Author for correspondence.
Email: DEK2@yandex.ru
ORCID iD: 0000-0002-2456-8165
SPIN-code: 3252-3029
Scopus Author ID: 12770589000
ResearcherId: C-2206-2012

MD, Dr. Sci. (Medicine), Professor of the Russian Academy of Sciences, Head of the Department of General and Special Morphology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

References

  1. Chanson M, Chandross KJ, Rook MB, et al. Gating characteristics of a steeply voltage-dependent gap junction channel in rat Schwann cells. J Gen Physiol. 1993;102(5):925–946. doi: 10.1085/jgp.102.5.925
  2. Chandross KJ, Spray DC, Kessler JA. Gap junctions and Schwann cells. In: Kanno Y, Kataoka K, Shiba Y, et al., editors. Intercellular Communication through Gap Junctions. Vol. 4. Amsterdam: Elsevier Science B.V.; 1995. P. 273–277. doi: 10.1016/B978-0-444-81929-1.50056-3
  3. Balice-Gordon RJ, Bone LJ, Scherer SS. Functional gap junctions in the Schwann cell myelin sheath. J Cell Biol. 1998;142(4):1095–1104. doi: 10.1083/jcb.142.4.1095
  4. Bergoffen J, Scherer SS, Wang S, et al. Connexin mutations in X-linked Charcot–Marie–Tooth disease. Science. 1993;262(5142):2039–2042. doi: 10.1126/science.8266101
  5. Scherer SS, Deschênes SM, Xu YT, et al. Connexin32 is a myelin-related protein in the PNS and CNS. J Neurosci. 1995;15(12):8281–8294. doi: 10.1523/JNEUROSCI.15-12-08281.1995
  6. Scherer SS, Xu YT, Nelles E, et al. Connexin32-null mice develop demyelinating peripheral neuropathy. Glia. 1998;24(1):8–20. doi: 10.1002/(sici)1098-1136(199809)24:1<8::aid-glia2>3.0.co;2-3
  7. Spray DC, Dermietzel R. X-linked dominant Charcot–Marie–Tooth disease and other potential gap-junction diseases of the nervous system. Trends Neurosci. 1995;18(6):256–262.
  8. Spray DC, Dermietzel R. Gap junctions in the nervous system. Heidelberg: Springer-Verlag; 1996. 317 р.
  9. Meier C, Dermietzel R, Davidson KG, et al. Connexin32-containing gap junctions in Schwann cells at the internodal zone of partial myelin compaction and in Schmidt–Lanterman incisures. J Neurosci. 2004;24(13):3186–3198. doi: 10.1523/JNEUROSCI.5146-03.2004
  10. Li J, Habbes HW, Eiberger J, et al. Analysis of connexin expression during mouse Schwann cell development identifies connexin29 as a novel marker for the transition of neural crest to precursor cells. Glia. 2007;55(1):93–103. doi: 10.1002/glia.20427
  11. Bortolozzi M. What’s the function of connexin 32 in the peripheral nervous system? Front Mol Neurosci. 2018;11:227. doi: 10.3389/fnmol.2018.00227
  12. Yoshimura T, Satake M, Kobayashi T. Connexin43 is another gap junction protein in the peripheral nervous system. J Neurochem. 1996;67(3):1252–1258. doi: 10.1046/j.1471-4159.1996.67031252.x
  13. Mambetisaeva ET, Gire V, Evans WH. Multiple connexin expression in peripheral nerve, Schwann cells, and Schwannoma cells. J Neurosci Res. 1999;57(2):166–175. doi: 10.1002/(SICI)1097-4547(19990715)57:2<166::AID-JNR2>3.0.CO;2-Y
  14. Zhao S, Spray DC. Localization of Cx26, Cx32 and Cx43 in myelinating Schwann cells of mouse sciatic nerve during postnatal development. In: Werner R, editor. Gap Junctions. Amsterdam: IOS Press; 1998. P. 198–202.
  15. Nagaoka T, Oyamada M, Okajima S, Takamatsu T. Differential expression of gap junction proteins connexin26, 32, and 43 in normal and crush-injured rat sciatic nerves. Close relationship between connexin43 and occludin in the perineurium. J Histochem Cytochem. 1999;47(7):937–948. doi: 10.1177/002215549904700711
  16. Jessen KR, Morgan L, Stewart HJ, Mirsky R. Three markers of adult non-myelin-forming Schwann cells, 217c(Ran-1), A5E3 and GFAP: development and regulation by neuron-Schwann cell interactions. Development. 1990;109(1):91–103. doi: 10.1242/dev.109.1.91
  17. Triolo D, Dina G, Lorenzetti I, et al. Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage. J Cell Sci. 2006;119(Pt 19):3981–3993. doi: 10.1242/jcs.03168
  18. Jessen KR, Mirsky R. Negative regulation of myelination: relevance for development, injury, and demyelinating disease. Glia. 2008;56(14):1552–1565. doi: 10.1002/glia.20761
  19. Jessen KR, Mirsky R. The repair Schwann cell and its function in regenerating nerves. J Physiol. 2016;594(13):3521–3531. doi: 10.1113/JP270874
  20. Jessen KR, Mirsky R. The success and failure of the Schwann cell response to nerve injury. Front Cell Neurosci. 2019;13:33. doi: 10.3389/fncel.2019.00033
  21. Zochodne DW. Neurobiology of peripheral nerve regeneration. New York: Cambridge University Press; 2008. 276 p.
  22. Fornaro M, Marcus D, Rattin J, Goral J. Dynamic environmental physical cues activate mechanosensitive responses in the repair Schwann cell phenotype. Cells. 2021;10(2):425. doi: 10.3390/cells10020425
  23. Taveggia C, Feltri ML. Beyond wrapping: canonical and noncanonical functions of Schwann cells. Annu Rev Neurosci. 2022;45:561–580. doi: 10.1146/annurev-neuro-110920-030610
  24. Cisterna BA, Arroyo P, Puebla C. Role of connexin-based gap junction channels in communication of myelin sheath in Schwann cells. Front Cell Neurosci. 2019;13:69. doi: 10.3389/fncel.2019.00069
  25. Sandri C, Van Buren JM, Akert K. Membrane morphology of the vertebrate nervous system. Prog Brain Res. 1977:46:1–384.
  26. Tetzlaff W. Tight junction contact events and temporary gap junctions in the sciatic nerve fibres of the chicken during Wallerian degeneration and subsequent regeneration. J Neurocytol. 1982;11:839–858. doi: 10.1007/BF01153522
  27. Chandross KJ, Kessler JA, Cohen RI, et al. Altered connexin expression after peripheral nerve injury. Mol Cell Neurosci. 1996;7(6):501–518. doi: 10.1006/mcne.1996.0036
  28. Chen ZL, Yu WM, Strickland S. Peripheral regeneration. Annu Rev Neurosci. 2007;30:209–233. doi: 10.1146/annurev.neuro.30.051606.094337
  29. Mirsky R, Woodhoo A, Parkinson DB, et al. Novel signals controlling embryonic Schwann cell development, myelination and dedifferentiation. J Peripher Nerv Syst. 2008;13(2):122–135. doi: 10.1111/j.1529-8027.2008.00168.x
  30. Balakrishnan A, Belfiore L, Chu TH, et al. Insights into the role and potential of Schwann cells for peripheral nerve repair from studies of development and injury. Front Mol Neurosci. 2021;13:608442. doi: 10.3389/fnmol.2020.608442
  31. Jessen KR, Mirsky R, Lloyd AC. Schwann cells: development and role in nerve repair. Cold Spring Harb Perspect Biol. 2015;7(7):a020487. doi: 10.1101/cshperspect.a020487
  32. Jessen KR, Arthur-Farraj P. Repair Schwann cell update: Adaptive reprogramming, EMT, and stemness in regenerating nerves. Glia. 2019;67(3):421–437. doi: 10.1002/glia.23532
  33. Boerboom A, Dion V, Chariot A, Franzen R. Molecular mechanisms involved in Schwann cell plasticity. Front Mol Neurosci. 2017;10:38. doi: 10.3389/fnmol.2017.00038

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2. Fig. 1. GFAP-immunopositive (a) and Cx43-immunopositive (b) cells in the distal segment of the rat sciatic nerve 7 days after injury. Serial slices. Topographic markers for sections: M — macrophage, C — vessel, * and ** — structures containing Cx43 (а) and not containing GFAP (b). Immunohistochemical reactions to GFAP (a) and Cx43 (b). Scale bar 20 µm

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3. Fig. 2. Cx43-immunopositive (a, b) and GFAP-immunopositive (c) structures in the rat sciatic nerve 7 days after injury. a — fragment of a blood vessel in the epineurium of the damaged nerve; b — Cx43-immunopositive process cells in the endoneurium; c — reparative Schwann cells. Confocal microscopy, immunohistochemical reaction for Cx43 (a, b) and GFAP (c) visualization using RRX fluorochrome, nuclei stained with nuclear fluorescent dye SYTOX Green. Scale bar 20 µm

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4. Fig. 3. Cx43-immunopositive cell in endoneurium 7 days after rat sciatic nerve injury. Immunofluorescent reaction for Cx43 (RRX) with additional staining of cell nuclei (SYTOX Green). Confocal laser microscopy. Orthogonal projection over a series of 16 planar images making up a Z-stack (3.9 µm) (a). Distribution of Cx43 along the depth of a histological section (b). Scale bar 10 µm

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