Thyroxine restores hippocampal neurogenesis and synaptogenesis in a male rat model of carbimazole-induced hypothyroidism: a histological study

Abstract

Abstract Background Adult-onset hypothyroidism has a deleterious effect on hippocampal cognitive and memory functions. This study was performed to evaluate the possible therapeutic effect of thyroxine on hippocampus degeneration in an adult male rat model of carbimazole-induced hypothyroidism and the potentiality of spontaneous recovery. Thirty-two adult male albino rats were divided equally into four groups, as follows: I (control group), II (hypothyroidism group) received carbimazole (20 mg/kg) orally once daily for 4 weeks; III (recovery group) rats were managed as in group II, then left untreated for an additional 4 weeks to assess spontaneous recovery; and IV (thyroxine-treated group): hypothyroidism was induced as in group II, then rats received levothyroxine (20 µg/kg/day) orally for 4 weeks. Rats and their corresponding controls were sacrificed after 4 weeks in group II and after 8 weeks in groups III and IV. The levels of T3, T4, and TSH were measured. Hematoxylin and Eosin staining of thyroid and hippocampal sections was performed. Additionally, toluidine blue staining and immunohistochemical staining for PCNA, GFAP, and synaptophysin were applied to hippocampus sections. Both morphometric measurements and statistical analysis were performed. Results Comparison of thyroxine-treated group with hypothyroidism and recovery groups revealed a significant reduction in TSH level and an increase in T3 and T4 levels, as well as improved histological architecture in both the thyroid and hippocampal sections. Hippocampal sections revealed a significant decrease in the mean area percent of GFAP, a significant increase in the mean number of PCNA-positive cells in the subgranular zone (SGZ); a niche for the adult neural stem cells (NSCs) in the hippocampus; and a significant increase in the mean area percent as well as the mean optical density of synaptophysin. Conclusion Hippocampal degeneration is induced by hypothyroidism and can be restored by thyroxine replacement therapy, probably through neuronal cell preservation, synaptogenesis, and stimulation of neurogenesis in SGZ. On the other hand, spontaneous recovery from this degeneration was inadequate.

Keywords

• Hypothyroidism
• Hippocampus
• Levothyroxine
• SGZ
• Neurogenesis
• PCNA