Cognitive dysfunction associated with activation of the mTOR signaling pathway after TSH suppression therapy in rats

Abstract

Thyroid stimulating hormone (TSH) suppression therapy after thyroid carcinoma surgery could lead to cognitive impairment. But, the possible mechanism of TSH suppression therapy impairs cognitive function is yet unknown. In this study, forty Wistar rats were randomized into the sham operation control (OC), total thyroidectomy (TD), thyroxine replacement therapy (TR), and TSH suppression therapy (TS) groups. We observed that compared to the OC group, escape latency on 1–4 days was significantly prolonged in the TD and TS groups, and the number of rats crossing the virtual platform was significantly reduced in the TD and TS groups. In the TD, TR, and TS groups, the residence time in the target quadrant was significantly decreased, while the activity distance in the target quadrant in the TD group was significantly decreased compared with OC group. In the TD and TS groups, the pyramidal cells in the hippocampal CA1 region showed a disordered arrangement. The cytoplasm was lightly stained, the cells were swollen and round, and spotty liquefaction necrosis could be observed. Compared to the OC group, hippocampal p-mTOR and p-p70s6k levels were significantly decreased in the TD group, while no significant changes were detected in the TR group. Hippocampal p-mTOR and p-p70s6k amounts in the TS group were significantly increased compared with OC group. These results indicated that TSH suppression therapy after total thyroidectomy in rats could impair cognitive function, which might be related to the activation of the mTOR signaling pathway and the damage and necrosis of hippocampal neurons.