Maternal marginal iodine deficiency delays cerebellar Bergmann glial cell development in rat offspring: Involvement of Notch signaling pathway.

During early pregnancy, iodine deficiency (ID) is linked to adverse effects on child motor and psychomotor function. Maternal marginal ID has become a common public health problem. It is unclear whether marginal ID influences the development of the cerebellum or its underlying mechanisms. Thus, the purpose of this study was to determine the effects of marginal ID on the development of cerebellar Bergmann glial cells (BGs) and investigate the activation of the Notch signaling pathway, which is crucial for the development and morphology of BGs. We treated Wistar rats with an ID diet (iodine content 60 ± 1.5 ng/g) supplemented with deionized water containing different concentrations of potassium iodide (KI) (183, 117, and 0 μg/L for the control, marginal ID, and severe ID groups, respectively) during pregnancy and lactation. We explored the morphology of the BGs by Golgi-Cox staining and immunofluorescence and investigated the Notch signaling pathway using western blot. Our results showed that the marginal ID and severe ID groups had decreased cerebellar BG fiber lengths (P < 0.05 and 0.01, respectively) and numbers (P < 0.01 for both) on postnatal day (PN) 7, PN14, and PN21 compared to the control group. Moreover, the data showed that severe ID significantly reduced Dll1, Notch1, RBP-Jκ, and BLBP protein levels at all three time points. Marginal ID slightly reduced the expression of Notch1 on PN7 (P < 0.05) and PN21 (P < 0.01), RBP-Jκ on PN14 (P < 0.01) and PN21 (P < 0.05), and BLBP on PN7 (P < 0.05). There was no significant difference in Dll1 protein levels between the marginal ID and control groups at any time point. Our study suggests that marginal ID leads to mild damage to BG morphogenesis in the cerebellum. The abnormal regulation of the Notch signaling pathway may be involved in the damage to BGs.