Expression of parvalbumin, osteopontin and glypican 4 in neurons of lumbar region distant from the epicenter of traumatic spinal cord injury

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Spinal cord injury (SCI) is manifested by pathologic changes in the areas significantly distant from the area of primary injury. In order to find new potential therapeutic targets to restore motor function, it is particularly relevant to identify the causes and mechanisms of these shifts in the lumbar spinal cord when injury occurs in the proximal spinal cord. On the model of dosed SCI the expression of Ca-binding protein parvalbumin (PARV), osteopontin (OPN) and glypican 4 (GPC4) in neurons of laminae VII, VIII and IX within segments L3–4 on 7 and 60 days of the experiment was studied. Laminas VII and IX show a decrease in the number of PARV+ neurons during the acute and chronic phase of SCI, which may indicate a decrease in calcium binding in ventral horn neurons at the level of segments L3–4. Decreased PARV expression in these neurons indicates an increased risk of their vulnerability and impaired motor function. The pattern of OPN expression in lumbar horn neurons distant from the epicenter of traumatic injury was studied for the first time. In all the studied laminae in the ventral horns of the gray matter, we did not observe shifts in the number of OPN+ neurons both in the acute and chronic phases of SCI. In lamina IX of the lumbar spinal cord, we found an increase in the number of GPC4+ neurons in the acute posttraumatic period, which can be regarded as a key positive adaptive reaction of neurons in the lumbar spinal cord remote from the epicenter of injury. The assessment of this reaction as positive is based on the data on the binding of GPC4 anchored on the neuron surface to various molecules with neuroprotective activity and stimulating neuroregeneration.

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Sobre autores

O. Tutova

Kazan (Volga region) Federal University

Email: ikabdesh@gmail.com
Rússia, Kazan

I. Kabdesh

Kazan (Volga region) Federal University

Autor responsável pela correspondência
Email: ikabdesh@gmail.com
Rússia, Kazan

Ya. Mukhamedshina

Kazan (Volga region) Federal University; Kazan State Medical University

Email: ikabdesh@gmail.com
Rússia, Kazan; Kazan

Yu. Chelyshev

Kazan (Volga region) Federal University; Kazan State Medical University

Email: ikabdesh@gmail.com
Rússia, Kazan; Kazan

Bibliografia

  1. Czeiter E, Pal J, Kovesdi E, Bukovics P, Luckl J, Doczi T, Buki A (2008) Traumatic axonal injury in the spinal cord evoked by traumatic brain injury. J Neurotrauma 25: 205–213. https://doi.org/10.1089/neu.2007.0331
  2. Freund P, Curt A, Friston K, Thompson A (2013) Tracking changes following spinal cord injury: Insights from neuroimaging. Neuroscientist 19: 116–128. https://doi.org/10.1177/1073858412449192
  3. Bisicchia E, Latini L, Cavallucci V, Sasso V, Nicolin V, Molinari M, D’Amelio M, Viscomi MT (2017) Autophagy Inhibition Favors Survival of Rubrospinal Neurons After Spinal Cord Hemisection. Mol Neurobiol 54: 4896–4907. https://doi.org/10.1007/s12035-016-0031-z
  4. Chelyshev Y (2022) More Attention on Segments Remote from the Primary Spinal Cord Lesion Site. Front Biosci – Landmark 27: 235. https://doi.org/10.31083/j.fbl2708235
  5. Nardone R, Trinka E (2015) Reorganization of spinal neural circuitry and functional recovery after spinal cord injury. Neural Regen Res 10: 201–202. https://doi.org/10.4103/1673-5374.152368
  6. Smith AC, Knikou M (2016) A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function. Neural Plast 2016: 1216258. https://doi.org/10.1155/2016/1216258
  7. Yang B, Zhang F, Cheng F, Ying L, Wang C, Shi K, Wang J, Xia K, Gong Z, Huang X, Yu C, Li F, Liang C, Chen Q (2020) Strategies and prospects of effective neural circuits reconstruction after spinal cord injury. Cell Death Dis 11: 439. https://doi.org/10.1038/s41419-020-2620-z
  8. Wang Y, Wu W, Wu X, Sun Y, Zhang YP, Deng LX, Walker MJ, Qu W, Chen C, Liu NK, Han Q, Dai H, Shields LBE, Shields CB, Sengelaub DR, Jones KJ, Smith GM, Xu XM (2018) Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery. Elife 7: e39016. https://doi.org/10.7554/eLife.39016
  9. Beauparlant J, Van Den Brand R, Barraud Q, Friedli L, Musienko P, Dietz V, Courtine G (2013) Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury. Brain 136: 3347–3361. https://doi.org/10.1093/brain/awt204
  10. Hou S, Duale H, Cameron AA, Abshire SM, Lyttle TS, Rabchevsky AG (2008) Plasticity of lumbosacral propriospinal neurons is associated with the development of autonomic dysreflexia after thoracic spinal cord transection. J Comp Neurol 509: 382–399. https://doi.org/10.1002/cne.21771
  11. Dougherty KJ, Hochman S (2008) Spinal cord injury causes plasticity in a subpopulation of lamina I GABAergic interneurons. J Neurophysiol 100: 212–223
  12. Matson KJE, Russ DE, Kathe C, Hua I, Maric D, Ding Y, Krynitsky J, Pursley R, Sathyamurthy A, Squair JW, Levi BP, Courtine G, Levine AJ (2022) Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons. Nat Commun 13: 5628. https://doi.org/10.1038/s41467-022-33184-1
  13. Antal M, Polgár E, Chalmers J, Minson JB, Llewellyn‐Smith I, Heizmann CW, Somogyi P (1991) Different populations of parvalbumin‐ and calbindin‐D28k‐immunoreactive neurons contain GABA and accumulate 3H‐D‐aspartate in the dorsal horn of the rat spinal cord. J Comp Neurol 314: 114–124. https://doi.org/10.1002/cne.903140111
  14. Laing I, Todd AJ, Heizmann CW, Schmidt HHHW (1994) Subpopulations of gabaergic neurons in laminae i-iii of rat spinal dorsal horn defined by coexistence with classical transmitters, peptides, nitric oxide synthase or parvalbumin. Neuroscience 61: 123–132. https://doi.org/10.1016/0306-4522(94)90065-5
  15. Chakrabarty S, Shulman B, Martin JH (2009) Activity-dependent codevelopment of the corticospinal system and target interneurons in the cervical spinal cord. J Neurosci 29: 8816–8827. https://doi.org/10.1523/JNEUROSCI.0735-09.2009
  16. Ma X, Miraucourt LS, Qiu H, Sharif-Naeini R, Khadra A (2023) Modulation of SK Channels via Calcium Buffering Tunes Intrinsic Excitability of Parvalbumin Interneurons in Neuropathic Pain: A Computational and Experimental Investigation. J Neurosci 43: 5608–5622. https://doi.org/10.1523/JNEUROSCI.0426-23.2023
  17. Veshchitskii A, Merkulyeva N (2023) Calcium-binding protein parvalbumin in the spinal cord and dorsal root ganglia. Neurochem Int 171: 105634. https://doi.org/10.1016/j.neuint.2023.105634
  18. Chen B, Li Y, Yu B, Zhang Z, Brommer B, Williams PR, Liu Y, Hegarty SV, Zhou S, Zhu J, Guo H, Lu Y, Zhang Y, Gu X, He Z (2018) Erratum: Reactivation of Dormant Relay Pathways in Injured Spinal Cord by KCC2 Manipulations Cell 174(3):521–535.e13. https://doi.org/10.1016/j.cell.2018.08.050
  19. Khalki L, Sadlaoud K, Lerond J, Coq JO, Brezun JM, Vinay L, Coulon P, Bras H (2018) Changes in innervation of lumbar motoneurons and organization of premotor network following training of transected adult rats. Exp Neurol 299: 1–14. https://doi.org/10.1016/j.expneurol.2017.09.002
  20. Antal M, Freund TF, Polgár E (1990) Calcium‐binding proteins, parvalbumin‐ and calbindin‐D28k‐immunoreactive neurons in the rat spinal cord and dorsal root ganglia: A light and electron microscopic study. J Comp Neurol 295: 467–484. https://doi.org/10.1002/cne.902950310
  21. Ren K, Ruda MA (1994) A comparative study of the calcium-binding proteins calbindin-D28K, calretinin, calmodulin and parvalbumin in the rat spinal cord. Brain Res Rev 19: 163–179. https://doi.org/10.1016/0165-0173(94)90010-8
  22. Fahandejsaadi A, Leung E, Rahaii R, Bu J, Geula C (2004) Calbindin-D28K, parvalbumin and calretinin in primate lower motor neurons. Neuroreport 15: 443–448. https://doi.org/10.1097/00001756-200403010-00012
  23. Shaw PJ, Eggett CJ (2000) Molecular factors underlying selective vulnerability of motor neurons to neurodegeneration in amyotrophic lateral sclerosis. J Neurol Suppl 247: 17–27. https://doi.org/10.1007/s004150050553
  24. Weng Y, Lu F, Li P, Jian Y, Xu J, Zhong T, Guo Q, Yang Y (2024) Osteopontin Promotes Angiogenesis in the Spinal Cord and Exerts a Protective Role Against Motor Function Impairment and Neuropathic Pain After Spinal Cord Injury. Spine (Phila Pa 1976) 49: E142–E151. https://doi.org/10.1097/BRS.0000000000004954
  25. Bei F, Lee HHC, Liu X, Gunner G, Jin H, Ma L, Wang C, Hou L, Hensch TK, Frank E, Sanes JR, Chen C, Fagiolini M, He Z (2016) Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell 164: 219–232. https://doi.org/10.1016/j.cell.2015.11.036
  26. Misawa H, Hara M, Tanabe S, Niikura M, Moriwaki Y, Okuda T (2012) Osteopontin is an alpha motor neuron marker in the mouse spinal cord. J Neurosci Res 90: 732–742. https://doi.org/10.1002/jnr.22813
  27. Morisaki Y, Niikura M, Watanabe M, Onishi K, Tanabe S, Moriwaki Y, Okuda T, Ohara S, Murayama S, Takao M, Uchida S, Yamanaka K, Misawa H (2016) Selective expression of osteopontin in ALS-resistant motor neurons is a critical determinant of late phase neurodegeneration mediated by matrix metalloproteinase-9. Sci Rep 6: 27354. https://doi.org/10.1038/srep27354
  28. Sarrazin S, Lamanna WC, Esko JD (2011) Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol 3: 1–33. https://doi.org/10.1101/cshperspect.a004952
  29. Litwack ED, Stipp CS, Kumbasar A, Lander AD (1994) Neuronal expression of glypican, a cell-surface glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan, in the adult rat nervous system. J Neurosci 14: 3713–3724. https://doi.org/10.1523/jneurosci.14-06-03713.1994
  30. Farhy-Tselnicker I, van Casteren ACM, Lee A, Chang VT, Aricescu AR, Allen NJ (2017) Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from Axons to Induce Functional Synapse Formation. Neuron 96: 428–445.e13. https://doi.org/10.1016/j.neuron.2017.09.053
  31. Kaur SP, Cummings BS (2019) Role of glypicans in regulation of the tumor microenvironment and cancer progression. Biochem Pharmacol 168: 108–118. https://doi.org/10.1016/j.bcp.2019.06.020
  32. Kamimura K, Maeda N (2021) Glypicans and Heparan Sulfate in Synaptic Development, Neural Plasticity, and Neurological Disorders. Front Neural Circuits 15: 595596. https://doi.org/10.3389/fncir.2021.595596
  33. Allen NJ, Bennett ML, Foo LC, Wang GX, Chakraborty C, Smith SJ, Barres BA (2012) Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature 486: 410–414. https://doi.org/10.1038/nature11059
  34. Yuzaki M (2018) Two Classes of Secreted Synaptic Organizers in the Central Nervous System. Annu Rev Physiol 80: 243–262. https://doi.org/10.1146/annurev-physiol-021317-121322
  35. Lee E, Chung WS (2019) Glial control of synapse number in healthy and diseased brain. Front Cell Neurosci 13: 42. https://doi.org/10.3389/fncel.2019.00042
  36. Kabdesh IM, Mukhamedshina YO, Arkhipova SS, Sabirov DK, Kuznecov MS, Vyshtakalyuk AB, Rizvanov AA, James V, Chelyshev YA (2022) Cellular and Molecular Gradients in the Ventral Horns With Increasing Distance From the Injury Site After Spinal Cord Contusion. Front Cell Neurosci 16. https://doi.org/10.3389/fncel.2022.817752
  37. McBride RL, Feringa ER (1992) Ventral horn motoneurons 10, 20 and 52 weeks after T-9 spinal cord transection. Brain Res Bull 28: 57–60. https://doi.org/10.1016/0361-9230(92)90230-U
  38. Yokota K, Kubota K, Kobayakawa K, Saito T, Hara M, Kijima K, Maeda T, Katoh H, Ohkawa Y, Nakashima Y, Okada S (2019) Pathological changes of distal motor neurons after complete spinal cord injury. Mol Brain 12: 1–15. https://doi.org/10.1186/s13041-018-0422-3
  39. García-Alías G, Torres-Espín A, Vallejo C, Navarro X (2010) Functional involvement of the lumbar spinal cord after contusion to T8 spinal segment of the rat. Restor Neurol Neurosci 28: 781–792. https://doi.org/10.3233/RNN-2010-0549
  40. Yokota K, Kubota K, Kobayakawa K, Saito T, Hara M, Kijima K, Maeda T, Katoh H, Ohkawa Y, Nakashima Y, Okada S (2019) Pathological changes of distal motor neurons after complete spinal cord injury. Mol Brain 12: 1–15. https://doi.org/10.1186/s13041-018-0422-3
  41. Spruill MM, Kuncl RW (2015) Calbindin-D28K is increased in the ventral horn of spinal cord by neuroprotective factors for motor neurons. J Neurosci Res 93: 1184–1191. https://doi.org/10.1002/jnr.23562
  42. Elliott JL, Snider WD (1995) Parvalbumin is a marker of ALS-resistant motor neurons. Neuroreport 6: 449–452. https://doi.org/10.1097/00001756-199502000-00011
  43. Oikari LE, Yu C, Okolicsanyi RK, Avgan N, Peall IW, Griffiths LR, Haupt LM (2020) HSPGs glypican-1 and glypican-4 are human neuronal proteins characteristic of different neural phenotypes. J Neurosci Res 98: 1619–1645. https://doi.org/10.1002/jnr.24666

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2. Fig. 1. Immunofluorescence analysis. Visualization of GPC4 expression in different laminae (VII, VIII, IX) of the anterior horns in the lumbar region (segments L3–4) of the rat spinal cord. Scale bar: 100 µm (10×).

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3. Fig. 2. The number of (a) PARV+, (b) OPN+, (c) GPC4+ neurons in the lamina VII of the anterior horns in the lumbar region (segments L3–4) of the intact and injured at the thoracic level (segment Th8) of the rat spinal cord on the 7th and 60th days after injury (7 and 60 dpi – days post injury); p < 0.05, Kruskal–Wallis test.

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4. Fig. 3. The number of (a) PARV+, (b) OPN+, (c) GPC4+ neurons in the VIII lamina of the anterior horns in the lumbar region (segments L3–4) of the intact and injured at the thoracic level (segment Th8) spinal cord of the rat on the 7th and 60th days after injury (7 and 60 dpi); p < 0.05, Kruskal–Wallis test.

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5. Fig. 4. The number of (a) PARV+, (b) OPN+, (c) GPC4+ neurons in the lamina IX of the anterior horns in the lumbar region (segments L3–4) of the intact and injured at the thoracic level (segment Th8) spinal cord of the rat on the 7th and 60th days after injury (7 and 60 dpi – days post injury); p < 0.05, Kruskal – Wallis test.

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6. Fig. 5. Changes in the integrated fluorescence intensity (MIF units – mean intensity of fluorescence) of GPC4 in the anterior horns of the lumbar region (segments L3–4) of the intact and injured at the level of the thoracic region (segment Th8) of the rat spinal cord on the 7th and 60th days after injury (7 and 60 dpi – days post injury); p < 0.05, Tukey test.

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7. Fig. 6. Immunofluorescence analysis visualizing the expression of (a) PARV (red), (b) OPN (yellow), and (c) GPC4 (red) in the anterior horn (lamina IX) of the lumbar region (segments L3–4) of the rat spinal cord. Scale bar: 50 μm (20×).

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