Effects of Excessive Iodine on the BDNF-TrkB Signaling Pathway and Related Genes in Offspring of EAT Rats

Abstract

Excess iodine can cause autoimmune thyroiditis (AIT) in women, but it is unclear whether this has any implications for neurodevelopmental mechanisms in offspring. We studied the effects of experimental autoimmune thyroiditis (EAT) rats with different amounts of iodine intake on offspring brain development via the brain-derived neurotrophic factor (BDNF)-tropomycin receptor kinase B (TrkB) signaling pathway, because BDNF plays an important role in neurodevelopment. Rats in three thyroglobulin (Tg) immunized groups with varying iodine intakes (Tg (100 µg/L iodine), Tg + High-iodine I group (Tg + HI, 20 mg/L iodine), and Tg + High-iodine II group (Tg + HII, 200 mg/L iodine)) were injected with 800 µg Tg once every 2 weeks for 3 times. Rats in the control group (NI, 100 µg/L iodine) were immunized with saline. Arsenic-cerium catalytic spectrophotometry was used to measure urine iodine levels. The lymphocytic infiltration in the thyroids was observed by histopathological studies. Thyroid autoantibodies levels were measured using radioimmunoassay. The norepinephrine (NE) contents were measured by an enzyme-linked immunosorbent assay. The levels of the BDNF-TrkB signaling pathway and related genes were measured by quantitative real-time PCR and Western blot. Urinary iodine levels increased as iodine intake increased. Lymphocytes were significantly aggravated in Tg-immunized rats. Serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) levels were clearly elevated in Tg-immunized rats. Tg-immune groups had significantly lower NE levels. The BDNF-TrkB signaling pathway and related gene mRNA and protein levels were found to be significantly lower in Tg-immune groups with higher iodine levels. Maternal AIT may reduce the levels of certain neurodevelopmental mechanisms in the offspring, such as the BDNF-TrkB signaling pathway and related factors, while excessive iodine consumption by the mother may exacerbate this effect.

Keywords: BDNF-TrkB signaling pathway; EAT; Iodine excess; Neurodevelopment.