A Mouse Model of Spaceflight Associated Neuro-ocular Syndrome Using One-Carbon Genetics Article Swipe
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· 2024
· Open Access
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· DOI: https://doi.org/10.1016/j.cdnut.2024.103728
· OA: W4400147997
Objectives: Spaceflight Associated Neuro-ocular Syndrome (SANS) includes an array of ophthalmic and neurologic signs and symptoms observed in a subset of astronauts after prolonged spaceflight. The etiology of these changes remains unknown. Data from spaceflight and bed rest studies provide evidence that the one-carbon (1C) metabolic pathway is involved in the risk of developing SANS. Specifically, it has been demonstrated that genetic variants of methionine synthase reductase (MTRR) A66G and serine hydroxymethyltransferase-1 (SHMT1) C1420T are associated with ophthalmic changes. Moreover, the magnitude of change in total retinal thickness (ΔTRT) in astronauts is greater for those with these genetic variants when combined with lower B-vitamin status (e.g., folate, vitamins B6 and B12, and riboflavin). Rodent research utilizing real and simulated spaceflight conditions has yet to provide a rodent model of SANS. Methods: In this study, mice with a genetic knock-out (KO) for SHMT1 are compared to age-matched WT mice fed either a folate-deficient (FD) or folate-sufficient (FS) diet. Optical coherence tomography (OCT) is performed to determine TRT. Blood is collected following OCT to assess B-vitamin status. Following the study, the mice will be euthanized, and ocular pathologies will be assessed via histological staining. Results: Preliminary analyses have indicated an effect of the diet on TRT (FS TRT = 202 μm vs. FD TRT = 243 μm). Additionally, TRT trended high in the SHMT KO fed the FD diet (TRT = 246 μm) as compared to WT on the same diet (TRT = 239 μm). Further OCT analyses are necessary before any conclusions can be drawn regarding observations as a result of diet, genetics, or a combination thereof. Conclusions: This study will evaluate the relationship between biochemical markers of disrupted one-carbon metabolism and total retinal thickness. Creating rodent models of SANS will allow us to systematically evaluate individual contributing factors of the spaceflight environment (radiation, microgravity, CO2, etc) that increase one's risk of developing SANS and allow for the testing and/or evaluation of countermeasures. Funding Sources: This work is funded by Texas A&M Institute for Advancing Health through Agriculture.
