Hyperthyroidism leads learning and memory impairment possibly via GRIN2B expression alterations

Abstract

The hippocampus as an important structure for learning and memory functions contains a high level of thyroid hormone receptors. Although there are numerous studies investigating the effects of thyroid hormones on cognitive dysfunction and psychiatric symptoms, the underlying molecular processes of these disorders have not yet been fully elucidated. In the present study, 24 male adult rats (4 months) were divided into 3 groups: control group, sham group and hyperthyroid group. Hyperthyroid group and sham group were treated with l-thyroxine or saline for 21 days. Each group was exposed to Morris water maze testing (MWMT), measuring their performance in a hidden-platform spatial task. After learning and memory tests, intracardiac blood was taken from the rats for serum thyroxine levels. Following blood collection, the rats were decapitated to isolate hippocampal tissue. GRIN2A, GRIN2B, BDNF, cFOS, Cdk5, cdk5r1 (p35), and cdk5r2 (p39) gene expression were evaluated using quantitative reverse transcriptase-PCR. Serum thyroxine level was found to be higher in hyperthyroid rats than in the control and sham groups. According to our MWMT findings, the memory performance of the hyperthyroid group was significantly impaired compared to the control and sham groups (p < 0.05). In the hippocampus, the GRIN2A gene expression level was decreased in the sham group, and the GRIN2B gene expression level was decreased in the sham and hyperthyroid groups compared to the control group (p < 0.05). There was no significant difference in other genes (p > 0.05). Hyperthyroidism impaired hippocampus-dependent spatial memory. Hyperthyroidism caused decreased level of GRIN2B gene expression in the hippocampus.