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Cited by 14Proteoglycans and glycosaminoglycans researchTraumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury Research

Changes in Brain Matrix Glycan Sulfation Associate With Reactive Gliosis and Motor Coordination in Mice With Head Trauma

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Alonge, Kimberly M., Herbert, Melanie J., Yagi, Mayumi, Cook, David G., Banks, William A., Logsdon, Aric F.·2021·Frontiers in Behavioral Neuroscience
DOI 10.3389/fnbeh.2021.745288PMC PMC8581466
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Abstract

Perineuronal nets (PNNs) are extracellular matrix (ECM) structures that enmesh and regulate neurocircuits involved in motor and sensory function. Maladaptive changes to the composition and/or abundance of PNNs have been implicated in preclinical models of neuroinflammation and neurocircuit destabilization. The central nervous system (CNS) is limited in its capacity to repair and reorganize neural networks following traumatic brain injury (TBI) and little is known about mechanisms of ECM repair in the adult brain after TBI. In this study, adult male C57BL/6 mice were subjected to a TBI via a controlled cortical impact (CCI) to the right motor and somatosensory cortices. At 7 days following CCI, histological analysis revealed a loss of Wisteria floribunda agglutinin (WFA) positive PNN matrices in the ipsilateral cortex. PNNs are comprised of chondroitin sulfate (CS) and dermatan sulfate (DS)-glycosaminoglycans (GAGs), the composition of which are known to influence neuronal integrity and repair. Using an innovative liquid chromatography tandem mass spectrometry (LC-MS/MS) method, we analyzed the relative abundance of six specific CS/DS-GAG isomers (Δ4S-, Δ6S-, Δ4S6S-, Δ2S6S-, Δ0S-CS, and Δ2S4S-DS) from fixed-brain sections after CCI injury. We report a significant shift in CS/DS-GAG sulfation patterns within the rostro-caudal extent of the injury site from mice exposed to CCI at 7 days, but not at 1 day, post-CCI. In the ipsilateral thalamus, the appearance of WFA+ puncta occurred in tandem with gliosis at 7 days post-CCI, but weakly colocalized with markers of gliosis. Thalamic WFA+ puncta showed moderate colocalization with neuronal ubiquitin C-terminal hydrolase L1 (UCHL1), a clinical biomarker for TBI injury. A shift in CS/DS-GAG sulfation was also present in the thalamus including an increase of 6S-CS, which is a specific isomer that associates with the presence of glial scarring. Upregulation of the 6S-CS-specific sulfotransferase (CHST3) gene expression was accompanied by reactive gliosis in both the ipsilateral cortex and thalamus. Moreover, changes in 6S-CS extracted from the thalamus positively correlated with deficits in motor coordination after CCI. Collectively, these data argue that CCI alters CS/DS-GAG sulfation in association with the spatiotemporal progression of neurorepair. Therapeutic interventions targeting restoration of CS/DS-GAG sulfation patterns may improve outcomes from TBI.

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Research works printed but not linked: 34

  1. Alonge K. M. Logsdon A. F. Murphree T. A. Banks W. A. Keene C. D. Edgar J. S.. (2019). Quantitative analysis of chondroitin sulfate disaccharides from human and rodent fixed brain tissue by electrospray ionization-tandem mass spectrometry. Glycobiology 29, 847– 860. 10.1093/glycob/cwz060 31361007 PMC6861844 · DOI · Paper page
  2. Alonge K. M. Mirzadeh Z. Scarlett J. M. Logsdon A. F. Brown J. M. Cabrales E.. (2020). Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats. Nat. Metab. 2, 1025– 1033. 10.1038/s42255-020-00275-6 32895577 PMC7572652 · DOI · Paper page
  3. Anderson M. A. Burda J. E. Ren Y. Ao Y. O’Shea T. M. Kawaguchi R.. (2016). Astrocyte scar formation aids central nervous system axon regeneration. Nature 532, 195– 200. 10.1038/nature17623 27027288 PMC5243141 · DOI · Paper page
  4. Bhowmick S. D’Mello V. Ponery N. Abdul-Muneer P. M. (2018). Neurodegeneration and sensorimotor deficits in the mouse model of traumatic brain injury. Brain Sci. 8: 11. 10.3390/brainsci8010011 29316623 PMC5789342 · DOI
  5. Biane J. S. Takashima Y. Scanziani M. Conner J. M. Tuszynski M. H. (2016). Thalamocortical projections onto behaviorally relevant neurons exhibit plasticity during adult motor learning. Neuron 89, 1173– 1179. 10.1016/j.neuron.2016.02.001 26948893 PMC4795975 · DOI
  6. Bradbury E. J. Moon L. D. Popat R. J. King V. R. Bennett G. S. Patel P. N.. (2002). Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416, 636– 640. 10.1038/416636a 11948352 · DOI · Paper page
  7. Brophy G. M. Mondello S. Papa L. Robicsek S. A. Gabrielli A. Tepas J.. (2011). Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids. J. Neurotrauma 28, 861– 870. 10.1089/neu.2010.1564 21309726 PMC3113451 · DOI
  8. Brown J. M. Xia J. Zhuang B. Cho K. S. Rogers C. J. Gama C. I.. (2012). A sulfated carbohydrate epitope inhibits axon regeneration after injury. Proc. Natl. Acad. Sci. U S A 109, 4768– 4773. 10.1073/pnas.1121318109 22411830 PMC3323996 · DOI · Paper page
  9. Burda J. E. Sofroniew M. V. (2014). Reactive gliosis and the multicellular response to CNS damage and disease. Neuron 81, 229– 248. 10.1016/j.neuron.2013.12.034 24462092 PMC3984950 · DOI
  10. Carulli D. Pizzorusso T. Kwok J. C. Putignano E. Poli A. Forostyak S.. (2010). Animals lacking link protein have attenuated perineuronal nets and persistent plasticity. Brain 133, 2331– 2347. 10.1093/brain/awq145 20566484 · DOI · Paper page
  11. Djerbal L. Lortat-Jacob H. Kwok J. (2017). Chondroitin sulfates and their binding molecules in the central nervous system. Glycoconj. J. 34, 363– 376. 10.1007/s10719-017-9761-z 28101734 PMC5487772 · DOI · Paper page
  12. Hamai A. Hashimoto N. Mochizuki H. Kato F. Makiguchi Y. Horie K.. (1997). Two distinct chondroitin sulfate ABC lyases. An endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides. J. Biol. Chem. 272, 9123– 9130. 10.1074/jbc.272.14.9123 9083041 · DOI
  13. Kwok J. C. Dick G. Wang D. Fawcett J. W. (2011). Extracellular matrix and perineuronal nets in CNS repair. Dev. Neurobiol. 71, 1073– 1089. 10.1002/dneu.20974 21898855 · DOI · Paper page
  14. Lee K. H. Mathews P. J. Reeves A. M. Choe K. Y. Jami S. A. Serrano R. E.. (2015). Circuit mechanisms underlying motor memory formation in the cerebellum. Neuron 86, 529– 540. 10.1016/j.neuron.2015.03.010 25843404 PMC4417109 · DOI
  15. Lin R. Kwok J. C. Crespo D. Fawcett J. W. (2008). Chondroitinase ABC has a long-lasting effect on chondroitin sulphate glycosaminoglycan content in the injured rat brain. J. Neurochem. 104, 400– 408. 10.1111/j.1471-4159.2007.05066.x 18005340 · DOI
  16. Lin R. Rosahl T. W. Whiting P. J. Fawcett J. W. Kwok J. C. (2011). 6-Sulphated chondroitins have a positive influence on axonal regeneration. PLoS One 6: e21499. 10.1371/journal.pone.0021499 21747937 PMC3128591 · DOI · Paper page
  17. Liu H. Povysheva N. Rose M. E. Mi Z. Banton J. S. Li W.. (2019). Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia. Proc. Natl. Acad. Sci. U S A 116, 4643– 4650. 10.1073/pnas.1821282116 30760601 PMC6410860 · DOI
  18. Logsdon A. F. Francis K. L. Richardson N. E. Hu S. J. Faber C. L. Phan B. A.. (2021). Decoding perineuronal net glycan sulfation patterns in the Alzheimer’s disease brain. Alzheimers Dement. [Online ahead of print]. 10.1002/alz.12451 34482642 PMC8897514 · DOI
  19. Logsdon A. F. Schindler A. G. Meabon J. S. Yagi M. Herbert M. J. Banks W. A.. (2020). Nitric oxide synthase mediates cerebellar dysfunction in mice exposed to repetitive blast-induced mild traumatic brain injury. Sci. Rep. 10: 9420. 10.1038/s41598-020-66113-7 32523011 PMC7287110 · DOI
  20. McGrath J. C. Drummond G. B. McLachlan E. M. Kilkenny C. Wainwright C. L. (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br. J. Pharmacol. 160, 1573– 1576. 10.1111/j.1476-5381.2010.00873.x 20649560 PMC2936829 · DOI · Paper page
  21. Miyata S. Kitagawa H. (2016). Chondroitin 6-sulfation regulates perineuronal net formation by controlling the stability of aggrecan. Neural Plast. 2016: 1305801. 10.1155/2016/1305801 27057358 PMC4738747 · DOI · Paper page
  22. Nadanaka S. Miyata S. Yaqiang B. Tamura J. I. Habuchi O. Kitagawa H. (2020). Reconsideration of the semaphorin-3A binding motif found in chondroitin sulfate using galnac4s-6st-knockout mice. Biomolecules 10: 1499. 10.3390/biom10111499 33143303 PMC7694144 · DOI · Paper page
  23. Pizzorusso T. Medini P. Berardi N. Chierzi S. Fawcett J. W. Maffei L. (2002). Reactivation of ocular dominance plasticity in the adult visual cortex. Science 298, 1248– 1251. 10.1126/science.1072699 12424383 · DOI · Paper page
  24. Prabhakar V. Capila I. Soundararajan V. Raman R. Sasisekharan R. (2009). Recombinant expression, purification and biochemical characterization of chondroitinase ABC II from proteus vulgaris. J. Biol. Chem. 284, 974– 982. 10.1074/jbc.M806630200 18849565 PMC2613618 · DOI
  25. Properzi F. Carulli D. Asher R. A. Muir E. Camargo L. M. van Kuppevelt T. H.. (2005). Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia. Eur. J. Neurosci. 21, 378– 390. 10.1111/j.1460-9568.2005.03876.x 15673437 · DOI
  26. Shida M. Mikami T. Tamura J. I. Kitagawa H. (2019). Chondroitin sulfate-D promotes neurite outgrowth by acting as an extracellular ligand for neuronal integrin αVβ3. Biochim. Biophys. Acta Gen. Subj. 1863, 1319– 1331. 10.1016/j.bbagen.2019.06.004 31181256 · DOI · Paper page
  27. Silver J. Miller J. H. (2004). Regeneration beyond the glial scar. Nat. Rev. Neurosci. 5, 146– 156. 10.1038/nrn1326 14735117 · DOI
  28. Spliid C. B. Toledo A. G. Salanti A. Esko J. D. Clausen T. M. (2021). Beware, commercial chondroitinases vary in activity and substrate specificity. Glycobiology 31, 103– 115. 10.1093/glycob/cwaa056 32573715 · DOI
  29. Tanaka Y. H. Tanaka Y. R. Kondo M. Terada S. I. Kawaguchi Y. Matsuzaki M. (2018). Thalamocortical axonal activity in motor cortex exhibits layer-specific dynamics during motor learning. Neuron 100, 244– 258.e12. 10.1016/j.neuron.2018.08.016 30174116 · DOI · Paper page
  30. Wang K. K. W. Kobeissy F. H. Shakkour Z. Tyndall J. A. (2021). Thorough overview of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein as tandem biomarkers recently cleared by US food and drug administration for the evaluation of intracranial injuries among patients with traumatic brain injury. Acute Med. Surg. 8: e622. 10.1002/ams2.622 33510896 PMC7814989 · DOI
  31. Wiley C. A. Bissel S. J. Lesniak A. Dixon C. E. Franks J. Beer Stolz D.. (2016). Ultrastructure of diaschisis lesions after traumatic brain injury. J. Neurotrauma 33, 1866– 1882. 10.1089/neu.2015.4272 26914973 PMC5079449 · DOI
  32. Yamagata T. Saito H. Habuchi O. Suzuki S. (1968). Purification and properties of bacterial chondroitinases and chondrosulfatases. J. Biol. Chem. 243, 1523– 1535. 5647268
  33. Yang S. Gigout S. Molinaro A. Naito-Matsui Y. Hilton S. Foscarin S.. (2021). Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Mol. Psychiatry. [Online ahead of print]. 10.1038/s41380-021-01208-9 34272488 PMC8758471 · DOI · Paper page
  34. Yi J. H. Katagiri Y. Susarla B. Figge D. Symes A. J. Geller H. M. (2012). Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice. J. Comp. Neurol. 520, 3295– 3313. 10.1002/cne.23156 22628090 PMC3806093 · DOI · Paper page

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Authors
Alonge, K. M., Herbert, M. J., Yagi, M., Cook, D. G., Banks, W. A., & Logsdon, A. F.
Affiliations
  • University of Washington (US)
  • VA Puget Sound Health Care System (US)
Corresponding author
Logsdon, Aric F.
ORCID
Venue
Frontiers in Behavioral Neuroscience
Publisher
Frontiers Media SA
Published
2021-10-28
Volume
15
Pages
745288-745288
ISSN
1662-5153 (ISSN-L)
DOI
10.3389/fnbeh.2021.745288
PMC
PMC8581466
OpenAlex
W3210773697
Cited by
14
References
3
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 2
FWCI
1.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (AG066509, AG046619, AG059088)
  • National Institute on Aging
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
perineuronal nets, chondroitin sulfate, dermatan sulfate, glycosaminoglycans, reactive gliosis, traumatic brain injury, controlled cortical impact, motor coordination, thalamus, UCHL1, CHST3, sulfotransferase, extracellular matrix repair, neuroinflammation, Wisteria floribunda agglutinin, motor cortex

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