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Osmotic Contribution of Synthesized Betaine by Choline Dehydrogenase Using In Vivo and In Vitro Models of Post-traumatic Syringomyelia.

Authors
  • Pukale, Dipak D1
  • Lazarenko, Daria2
  • Aryal, Siddhartha R3
  • Khabaz, Fardin1, 2
  • Shriver, Leah P4, 5, 6
  • Leipzig, Nic D1, 3
  • 1 Department of Chemical, Biomolecular, and Corrosion Engineering, University of Akron, Akron, OH 44325 USA.
  • 2 School of Polymer Science and Polymer Engineering, The University of Akron, Akron, OH 44325 USA.
  • 3 Department of Biomedical Engineering, The University of Akron, Akron, OH 44325 USA.
  • 4 Department of Chemistry, Washington University, Saint Louis, MO 63130 USA.
  • 5 Department of Medicine, Washington University, Saint Louis, MO 63130 USA.
  • 6 Center for Metabolomics and Isotope Tracing, Washington University, Saint Louis, MO 63130 USA.
Type
Published Article
Journal
Cellular and molecular bioengineering
Publication Date
Feb 01, 2023
Volume
16
Issue
1
Pages
41–54
Identifiers
DOI: 10.1007/s12195-022-00749-5
PMID: 36660584
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Syringomyelia (SM) is a debilitating spinal cord disorder in which a cyst, or syrinx, forms in the spinal cord parenchyma due to congenital and acquired causes. Over time syrinxes expand and elongate, which leads to compressing the neural tissues and a mild to severe range of symptoms. In prior omics studies, significant upregulation of betaine and its synthesis enzyme choline dehydrogenase (CHDH) were reported during syrinx formation/expansion in SM injured spinal cords, but the role of betaine regulation in SM etiology remains unclear. Considering betaine's known osmoprotectant role in biological systems, along with antioxidant and methyl donor activities, this study aimed to better understand osmotic contributions of synthesized betaine by CHDH in response to SM injuries in the spinal cord. A post-traumatic SM (PTSM) rat model and in vitro cellular models using rat astrocytes and HepG2 liver cells were utilized to investigate the role of betaine synthesis by CHDH. Additionally, the osmotic contributions of betaine were evaluated using a combination of experimental as well as simulation approaches. In the PTSM injured spinal cord CHDH expression was observed in cells surrounding syrinxes. We next found that rat astrocytes and HepG2 cells were capable of synthesizing betaine via CHDH under osmotic stress in vitro to maintain osmoregulation. Finally, our experimental and simulation approaches showed that betaine was capable of directly increasing meaningful osmotic pressure. The findings from this study demonstrate new evidence that CHDH activity in the spinal cord provides locally synthesized betaine for osmoregulation in SM pathophysiology. The online version of this article contains supplementary material available 10.1007/s12195-022-00749-5. © The Author(s) under exclusive licence to Biomedical Engineering Society 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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