The effects of PPARγ agonists on long-term potentiation and apoptosis in the hippocampus area of juvenile hypothyroid rats

Abstract The aim of the present study was to evaluate the effect of rosiglitazone (RSG) or pioglitazone (POG) on the synaptic plasticity, neuronal apoptosis and brain-derived neurotrophic factor (BDNF) and nitric oxide(NO) metabolites in the hippocampus of juvenile hypothyroid rats. The animals were divided into four groups: (1) control, (2) propylthiouracil (PTU), (3) PTU–POG and (4) PTU–RZG. A 0.05% dose of PTU was administered in drinking water for 42 consecutive days. The POG (20 mg/ kg) and the RSG (4 mg/kg) were administered by intraperitoneal (IP) injection on a daily basis. To evaluate synaptic plasticity, we conducted long-term potentiation (LTP) in the Cornuammonist 1 (CA1) area of the hippocampus by high-frequency stimulation of the Schaffer collateral pathway. Then, the hippocampal tissues were collected to determine BDNF and NO levels. In addition, 5 animals from each group also were treated and the brains of animals were collected for apoptosis studies. PTU administration decreased slope, slope 10–90%, and amplitude of fEPSP compared to the control group. Injection of RSG or POG increased the slope, slope 10–90%, and amplitude of fEPSP in the PTU-POG or PTU-RSG groups in comparison to the PTU group. TUNEL positive neurons and NO metabolites in the hippocampus of the PTU group were higher than that of the control. PTU administration attenuated BDNF content, and RSG or POG increased BDNF content in PTU–POG or PTU–RSG groups. Treatment of the rats by POG or RSG decreased apoptotic neurons and NO metabolites in the hippocampus of PTU–POG or PTU–RSG groups compared to the PTU group. The results of this study revealed that POG or RSG normalized LTP impairment, neuronal apoptosis, and improved BDNF content in the hippocampal tissue of juvenile hypothyroid rats.