Excess Thyroid Hormone Inhibits Embryonic Neural Stem/Progenitor Cells Proliferation and Maintenance through STAT3 Signalling Pathway

Abstract

Hyperthyroidism is prevalent during pregnancy, but little is known about the effects of excess thyroid hormone on the development of embryonic neural stem/progenitor cells (NSCs), and the mechanisms underlying these effects. Previous studies indicate that STAT3 plays a crucial role in determining NSC fate during neurodevelopment. In this study, we investigated the effects of a supraphysiological dose of 3,5,3'-L-triiodothyronine (T3) on the proliferation and maintenance of NSCs derived from embryonic day 13.5 mouse neocortex, and the involvement of STAT3 in this process. Our results suggest that excess T3 treatment inhibits NSC proliferation and maintenance. T3 decreased tyrosine phosphorylation of JAK1, JAK2 and STAT3, and subsequently inhibited STAT3-DNA binding activity. Furthermore, proliferation and maintenance of NSCs were decreased by inhibitors of JAKs and STAT3, indicating that the STAT3 signalling pathway is involved in the process of NSC proliferation and maintenance. Taken together, these results suggest that the STAT3 signalling pathway is involved in the process of T3-induced inhibition of embryonic NSC proliferation and maintenance. These findings provide data for understanding the effects of hyperthyroidism during pregnancy on fetal brain development, and the mechanisms underlying these effects.

Exposure to 1800 MHz radiofrequency radiation impairs neurite outgrowth of embryonic neural stem cells

“…BrdU incorporation was used to detect cell proliferation as previously described51. Briefly, eNSCs (1.0 × 10 5  cells/ml) were exposed to RF-EMF for the indicated number of days.…”

Thyroid Hormone-Otx2 Signaling Is Required for Embryonic Ventral Midbrain Neural Stem Cells Differentiated into Dopamine Neurons

“…The effects of T3 on the proliferation of embryonic neural stem cells (eNSCs) were studied by a Colorimetric Cell-Counting Kit-8 (CCK-8; Dojindo) assay and 5-bromo-2-deoxyuridine (BrdU) incorporation, as previously described [32].…”

“…Western blot analysis was performed and quantified with an Odyssey system (LI-COR), as previously described [32]. The primary antibodies used for western blot analysis were the rabbit anti-mouse TH antibody (1:1,000; Abcam), rabbit or goat anti-mouse DAT antibody (1:1,000; Santa Cruz), rabbit anti-mouse Otx2 antibody (1:1,000; Santa Cruz), rabbit antimouse Ngn2 antibody (1:1,000; Santa Cruz), rabbit anti-mouse Nurr1 antibody (1:1,000; Santa Cruz), and mouse anti-mouse b-actin antibody (1:5,000; Sigma-Aldrich).…”

Maternal-Fetal Thyroid Interactions

“…DIII produces rT3 and T2 from T4 and T3, respectively [1,73,83]. T3 binds to nuclear TRs, TR and TR , that activate transcription by binding, generally as heterodimers with the retinoid X receptor (RXR) ( Table 5) [87], to thyroid hormone response elements (TREs) located in regulatory regions of target genes [84]. Activity is regulated by an exchange of corepressor (CoR) and coactivator (CoA) complexes.…”

“…TRs can also regulate the activity of genes that do not contain a TRE through "cross-talk" with other transcription factors (TF) that stimulate target gene expression [28,86]. Both receptors and coregulators are targets for phosphorylation (P) by signal transduction pathways stimulated by hormones and growth factors [84,85]. Thus, the nuclear actions of T3 are sensitive to inhibitors of transcription and translation and have a latency of hours to days [9,73].…”