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Relationship between thyroid hormones and associated metabolites and gene expression bioindicators in the serum of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis

ABSTRACT: Anuran metamorphosis is characterized by profound morphological changes including remodeling of tissues and organs. Here we investigate serum of Rana [Lithobates] catesbeiana (n=5-10) across seven distinct postembryonic stages beginning with premetamorphic tadpole (Gosner stage 31-33) and continuing through metamorphosis to a juvenile frog (Gosner stage 46). Using a sensitive nanoLC-Orbitrap system an untargeted analysis workflow was applied. Among 6,062 detected endogenous metabolites, 421 showed significant metamorphosis-dependent concentration dynamics. Among these potential bioindicators were several prostaglandins and other eicosanoids, some steroid hormones including testosterone, and several carnitines. These data provide a necessary context for interpreting developmental processes and potential molecular crosstalk mechanisms. Furthermore, this provides a solid foundation from which alternative bioindicators of metamorphosis may be chosen as feasible endpoints in future risk assessment of chemicals and their potency for causing developmental toxicity.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rana Catesbeiana (ncbitaxon:8400)

SUBMITTER: Martin Hansen

PROVIDER: MSV000090714 | MassIVE | Tue Nov 15 04:46:00 GMT 2022

REPOSITORIES: MassIVE

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Project description:BackgroundAltered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aβ) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aβ and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aβ and tau deposition.MethodsThis cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET.ResultsNo associations were found between either thyroid hormones or TSH and Aβ and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aβ on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aβ deposition was not significant, whereas the interaction between fT3 and Aβ deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aβ and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aβ on tau deposition.ConclusionOur findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aβ and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aβ-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.

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Relationship between thyroid hormones and associated metabolites and gene expression bioindicators in the serum of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis

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