Hypothyroidism increases cyclooxygenase-2 levels and pro-inflammatory response and decreases cell proliferation and neuroblast differentiation in the hippocampus

The present study investigated the effects of hypothyroidism on cyclooxygenase-2 (COX-2) and pro-inflammatory cytokines in the dentate gyrus to elucidate the roles of COX-2 in the hypothyroid hippocampus. Hypothyroidism was induced in rats by treating with 0.03% 2-mercapto-1-methyl-imidazole dissolved in drinking water for 5 weeks. The animals were sacrificed at 12 weeks of age. Hypothyroidism rats exhibited decreased triiodothyronine and thyroxine levels in the serum, while the levels of thyroid-stimulating hormone and the weight of thyroid glands were significantly higher in the hypothyroid rats compared with those in the vehicle-treated group. COX-2 immunoreactivity was significantly increased in the hippocampal CA2/3 region and the dentate gyrus compared with the vehicle-treated group. Levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were significantly higher in the hippocampal homogenates of hypothyroid rats. Cell proliferation and neuroblast differentiation based on Ki67 and doublecortin immunohistochemistry were decreased in the dentate gyrus of hypothyroid rats compared with those in the vehicle-treated group. These results suggested that hypothyroidism-mediated COX-2 expression affected hippocampal plasticity by upregulating the levels of pro-inflammatory cytokines in the hippocampus. Therefore, COX-2 may be suggested as a candidate molecule for preventing hypothyroidism-induced neurological side effects.