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Abstract Background and aim of work: Adult-onset hypothyroidism has deleterious effect on hippocampal cognitive and memory functions. So, this work was planned to evaluate the therapeutic potential effect of thyroxine on hippocampal degeneration in male rat model of carbimazole-induced hypothyroidism. Material and Methods: Thirty-six adult male albino rats were used in this study. Rats were divided into three groups: group {u2160}=control group, group II in which hypothyroidism was induced using carbimazole given orally at a dose of 20 mg/kg, every other day, using a gastric tube for 4 weeks. This group was subdivided into subgroup IIa in which rats were sacrificed after 4 weeks to confirm hypothyroidism and subgroup IIb in which rats were sacrificed after further 4 weeks (total of 8 weeks duration) to assess spontaneous recovery from carbimazole treatment. group III in which hypothyroidism was induced by the same regimen as in group II using carbimazole for 4 weeks then rats received levothyroxine at a dose of 20 microgram/kg/day orally, using a gastric tube, for further 4 weeks (total duration of 8 weeks). T3, T4 and TSH levels were measured. Hippocampal and thyroid specimens were processed for Hematoxylin and Eosin. In addition, hippocampal sections were stained with toluidine blue and immunohistochemical staining for GFAP, PCNA and synaptophysin. Results: As compared to the non-treated group, the treated group exhibited significant reduction in TSH levels and increase in T3 and T4 levels, improved histological architecture of both thyroid and hippocampal sections. Hippocampal sections revealed significant decrease in area % of GFAP, significant increase in number of PCNA positive cells in subgranular zone and significant increase in area % as well as optical density of synaptophysin |