Effects of hypothyroidism on cell proliferation and neuroblasts in the hippocampal dentate gyrus in a rat model of type 2 diabetes

We observed how the hypothyroid state affects diabetic states and modifies cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG). For this, 0.03% methimazole, an anti-thyroid drug, was administered to 7-week-old, pre-diabetic Zucker diabetic fatty (ZDF) rats by drinking water for 5 weeks, and the animals were sacrificed at 12 weeks of age. At this age, corticosterone levels were significantly increased in the ZDF rats compared to those in the control (Zucker lean control, ZLC) rats. Methimazole (methi) treatment in the ZDF rats (ZDF-methi rats) significantly decreased corticosterone levels and diabetes-induced hypertrophy of adrenal glands. In the DG, Ki67 (a marker for cell proliferation)- and doublecortin (DCX, a marker for neuronal progenitors)-immunoreactive cells were much lower in the ZDF rats than those in the ZLC rats. However, in ZDF-methi rats, numbers of Ki67- and DCX-immunoreactive cells were similar to those in the ZLC rats. These suggest that methi significantly reduces diabetes-induced hypertrophy of the adrenal gland and alleviates the diabetes-induced reduction of cell proliferation and neuronal progenitors in the DG.