SGLT2 Inhibition Attenuates Hippocampal Injury and Cognitive Impairment in Adult-Onset Hypothyroidism
Abstract
Thyroid hormones play a critical role in the maturation of developing brain regions. The aim of this study is to determine the effects of the SGLT2 inhibitor empagliflozin on learning and memory, locomotor activity, neuroinflammation, and oxidative stress levels in adult rats with hypothyroidism induced by propylthiouracil administration. 60 adult male Sprague-Dawley rats (250-350 g) were used in the study. The rats were randomly divided into 5 groups of 12 each: Con, PTU, Vehicle, EMP, and PTU+EMP. The Con and EMP groups were allowed free access to drinking water. For the PTU, Vehicle, and PTU+EMP groups, propylthiouracil was added to the rats' drinking water at a concentration of 0.05% w/v for 21 days. Starting from day 15, the EMP and PTU+EMP groups received i.p. empagliflozin injections at a dose of 10 mg/kg/day for 7 days, while the Vehicle group received empagliflozin solvent (DMSO, 5% w/w). Morris water maze test and open field test were performed. SOD and CAT enzyme activities, GSH, and MDA levels were determined from serum samples. CREB and nNOS levels and p-CREB immunoreactivity were examined in the hippocampus tissue using immunohistochemical methods. In the PTU group, locomotor activity decreased, and anxiety-like behaviors were observed. Escape latency (EL) was prolonged, and time spent in the target quadrant (TSTQ) decreased. Antioxidant enzyme activities decreased while MDA levels increased. Significant reductions in CREB, p-CREB, and nNOS levels, which are…
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