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

Dipak D Pukale; Daria Lazarenko; Siddhartha R Aryal; Fardin Khabaz; Leah P Shriver; Nic D Leipzig

doi:10.1007/s12195-022-00749-5

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

Cell Mol Bioeng. 2022 Nov 27;16(1):41-54. doi: 10.1007/s12195-022-00749-5. eCollection 2023 Feb.

Authors

Dipak D Pukale¹, Daria Lazarenko², Siddhartha R Aryal³, Fardin Khabaz^{1

2}, Leah P Shriver^{4

5

6}, Nic D Leipzig^{1

3}

Affiliations

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.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: The findings from this study demonstrate new evidence that CHDH activity in the spinal cord provides locally synthesized betaine for osmoregulation in SM pathophysiology.

Supplementary information: The online version of this article contains supplementary material available 10.1007/s12195-022-00749-5.

Keywords: Betaine; Choline dehydrogenase (CHDH); Osmoregulation; Osmotic pressure; Post-traumatic syringomyelia; Syrinx.

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