Optimized Mass Spectrometry Detection of Thyroid Hormones and Polar Metabolites in Rodent Cerebrospinal Fluid

Abstract

BackgroundThyroid hormones (TH) are required for brain development and function. Cerebrospinal fluid (CSF), which bathes the brain and spinal cord, contains TH as free or transthyretin (TTR)-bound. Tight thyroid hormone level regulation in the central nervous system is essential for developmental gene expression that governs neurogenesis, myelination, and synaptogenesis. This integrated function of TH highlights the importance of developing precise and reliable methods for assessing TH levels in CSF. Methods: we report an optimized LC-MS based method to measure thyroid hormones in rodent CSF and serum, applicable to both fresh and frozen samples. Results: We find distinct differences in CSF thyroid hormone in pregnant dams vs. non-pregnant adults and in embryonic vs. adult CSF. Further, targeted LC-MS metabolic profiling uncovers distinct central carbon metabolism in the CSF of these populations. Conclusions: TH detection and metabolite profiling of related metabolic pathways open new avenues of rigorous research into CSF thyroid hormone and will inform future studies on metabolic alterations in CSF during normal development.