Dataset Information

Axonal T3 uptake and transport can trigger thyroid hormone signaling in the brain.

ABSTRACT: The development of the brain, as well as mood and cognitive functions, are affected by thyroid hormone (TH) signaling. Neurons are the critical cellular target for TH action, with T3 regulating the expression of important neuronal gene sets. However, the steps involved in T3 signaling remain poorly known given that neurons express high levels of type 3 deiodinase (D3), which inactivates both T4 and T3. To investigate this mechanism, we used a compartmentalized microfluid device and identified a novel neuronal pathway of T3 transport and action that involves axonal T3 uptake into clathrin-dependent, endosomal/non-degradative lysosomes (NDLs). NDLs-containing T3 are retrogradely transported via microtubules, delivering T3 to the cell nucleus, and doubling the expression of a T3-responsive reporter gene. The NDLs also contain the monocarboxylate transporter 8 (Mct8) and D3, which transport and inactivate T3, respectively. Notwithstanding, T3 gets away from degradation because D3's active center is in the cytosol. Moreover, we used a unique mouse system to show that T3 implanted in specific brain areas can trigger selective signaling in distant locations, as far as the contralateral hemisphere. These findings provide a pathway for L-T3 to reach neurons and resolve the paradox of T3 signaling in the brain amid high D3 activity.

SUBMITTER: Salas-Lucia F

PROVIDER: S-EPMC10241515 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Axonal T3 uptake and transport can trigger thyroid hormone signaling in the brain.

Salas-Lucia Federico F Fekete Csaba C Sinkó Richárd R Egri Péter P Rada Kristóf K Ruska Yvette Y Gereben Balázs B Bianco Antonio C AC

eLife 20230519

The development of the brain, as well as mood and cognitive functions, are affected by thyroid hormone (TH) signaling. Neurons are the critical cellular target for TH action, with T3 regulating the expression of important neuronal gene sets. However, the steps involved in T3 signaling remain poorly known given that neurons express high levels of type 3 deiodinase (D3), which inactivates both T4 and T3. To investigate this mechanism, we used a compartmentalized microfluid device and identified a ...[more]

PMID: 37204837

Similar Datasets

Project description:Background The role of thyroid hormones is crucial in the response to stress and critical illness, which has been reported to be closely associated with a poor prognosis in patients admitted to the intensive care unit (ICU). This study aimed to explore the relationship between thyroid hormone and prognosis in septic shock patients. Methods A total of 186 patients with septic shock were enrolled in the analytical study between December 2014 and September 2022. The baseline variables and thyroid hormone were collected. The patients were divided into survivor group and non-survivor group according to whether they died during the ICU hospitalization. Among 186 patients with septic shock, 123 (66.13%) were in the survivor group and 63 (33.87%) were in the non-survivor group. Results There were significant differences in the indictors of free triiodothyronine (FT3) (p = 0.000), triiodothyronine (T3) (p = 0.000), T3/FT3 (p = 0.000), acute physiology and chronic health evaluation II score (APACHE II) (p = 0.000), sequential organ failure assessment score (SOFA) (p = 0.000), pulse rate (p = 0.020), creatinine (p = 0.008), PaO2/FiO2 (p = 0.000), length of stay (p = 0.000) and hospitalization expenses (p = 0.000) in ICU between the two groups. FT3 [odds ratio (OR): 1.062, 95% confidence interval(CI): (0.021, 0.447), p = 0.003], T3 (OR: 0.291, 95% CI: 0.172-0.975, p = 0.037) and T3/FT3 (OR: 0.985, 95% CI:0.974-0.996, p = 0.006) were independent risk factors of the short-term prognosis of septic shock patients after adjustment. The areas under the receiver operating characteristic curves for T3 was associated with ICU mortality (AUC = 0.796, p < 0.05) and was higher than that for FT3 (AUC = 0.670, p < 0.05) and T3/FT3 (AUC = 0.712, p < 0.05). A Kaplan-Meier curve showed that patients with T3 greater than 0.48 nmol/L had a significantly higher survival rate than the patients with T3 less than 0.48 nmol/L. Conclusions The decrease in serum level of T3 in patients with septic shock is associated with ICU mortality. Early detection of serum T3 level could help clinicians to identify septic shock patients at high risk of clinical deterioration.

Dataset Information

Axonal T3 uptake and transport can trigger thyroid hormone signaling in the brain.

Publications

Axonal T3 uptake and transport can trigger thyroid hormone signaling in the brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets