Perinatal thyroid hormone deficiency leads to oxidative stress-induced neuronal damage and activation of astrocytes in rat hippocampus: Neuroprotective effect of exercise

Abstract

Thyroid hormones play a crucial role in proper brain development. This study examined the effects of developmental thyroid hormone deficiency on neuronal survival, glial fibrillary acidic protein (GFAP)-positive cells, and oxidative stress biomarkers in the hippocampus of congenital hypothyroid rats. The effectiveness of treadmill exercise in attenuating oxidative stress-induced neuronal damage and astrocyte activation was also evaluated. Pregnant Wistar rats in the hypothyroid group received propylthiouracil in their drinking water from gestational day 6 until weaning, while control dams received only tap water. Then, male offspring from both groups were further divided into two sub-groups: with or without four weeks of treadmill exercise. After sacrifice, the right hemispheres were processed for cresyl violet staining and immunohistochemistry, while the left hippocampi were used for biochemical assays. Results showed a reduced number of neurons and an increased number of GFAP-positive cells in the CA1 region of hypothyroid rats, with no significant changes in the CA3 region. Additionally, congenital hypothyroidism was associated with increased malondialdehyde levels, decreased glutathione levels, and reduced superoxide dismutase and catalase activity in the hippocampus. Treadmill exercise reduced astrocyte activation and protected neurons by inhibiting oxidative stress. Collectively, our results indicate that congenital thyroid hormone deficiency triggers astrocyte activation and compromises neuronal survival in the CA1 region by inducing oxidative stress. Exercise may serve as a beneficial supplementary treatment for attenuating oxidative stress-induced neuronal damage in congenital hypothyroidism.