Background
Variable mechanisms are implicated in syrinx development, and this process is not fully understood. Our recent work in a post-traumatic syringomyelia (PTSM) rat model supports the theory that syrinx expansion may be due to fluid disturbance via betaine osmolyte upregulation and dysregulation of its associated channel betaine/GABA transporter (BGT-1). The role of betaine as an osmoprotectant has been studied extensively in plant and bacterial cells. Also, mammalian kidney and liver cells show the osmoprotectant role of betaine, however, there is no specific study of betaine osmoregulation in the central nervous system (CNS) especially connected to disease states. The primary goal of this research is to reveal the role of local betaine regulation on syrinx dynamics and to discover drugs that can target both betaine and tonicity regulation for the treatment of syringomyelia (SM).
Methods
Studies were designed to pharmacologically target betaine regulation via endogenous synthesis by choline dehydrogenase (CHDH) and transport through BGT-1 to understand the impact on biological fluid transport both in vitro and in vivo using a rat PTSM model.
Results
Data shows that in injured PTSM animals betaine is likely synthesized by CHDH in the spinal cord parenchyma, corresponding to upregulation of its transporter BGT-1 and other related markers as compared to sham and no treatment animals. Also, these changes were directly associated with the development of significant syrinxes. We have data to implicate astrocytes in these processes, and are currently performing sensitive in vitro assays to confirm betaine synthesis and transport.
Discussion and Conclusions
Our data to date suggests that SM development is due in part to dysregulation of betaine metabolism and transport, resulting in abnormal fluid accumulation within the spinal cord to accelerate syrinx expansion. Pharmacologically targeting betaine regulation via local endogenous synthesis by CHDH and/or transport through BGT-could impact biological fluid transport to lessen the impact of SM.