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PPARγ 激动剂对幼年甲状腺功能减退大鼠海马区长时程增强和细胞凋亡的影响。

The effects of PPARγ agonists on long‑termpotentiation and apoptosis in the hippocampusarea of juvenile hypothyroid rats.

机构信息

Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Anatomical Sciences, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran.

出版信息

Acta Neurobiol Exp (Wars). 2024 Jun 26;84(2):153-164. doi: 10.55782/ane-2024-2451.

DOI:10.55782/ane-2024-2451
PMID:39087839
Abstract

The aim of the present study was to evaluate the effect of rosiglitazone (RSG) or pioglitazone (POG) on the synaptic plasticity, neuronal apoptosis, brain-derived neurotrophic factor (BDNF), and nitric oxide (NO) metabolites in the hippocampus of juvenile hypothyroid rats. The animals were divided into four groups: control; propylthiouracil (PTU), 0.05% dose in drinking water for 42 days; PTU-POG; and PTU-RSG. The POG (20 mg/kg) and the RSG (4 mg/kg) were administered by IP injection. We conducted long‑term potentiation (LTP) in the cornu ammonis 1 area of the hippocampus using high‑frequency stimulation of the Schaffer collateral pathway. Then, the hippocampal tissues were collected to determine BDNF and NO levels and the degree of apoptosis. PTU administration decreased the slope (10-90%) and amplitude of the fEPSPs compared to control. Injection of RSG or POG increased the slope, slope (10-90%), and amplitude of the fEPSP in the PTU‑POG or PTU‑RSG groups compared to the PTU group. TUNEL‑positive neurons and NO metabolites in the hippocampus of the PTU group were higher than those of the control group. RSG or POG increased BDNF content in PTU-POG or PTU-RSG groups. Treatment of the rats with POG or RSG decreased apoptotic neurons and NO metabolites in the hippocampus of PTU-POG or PTU-RSG groups, respectively, compared to the PTU group. This study's results revealed that POG or RSG normalized LTP impairment, neuronal apoptosis, and improved BDNF content in the hippocampal tissue of juvenile hypothyroid rats.

摘要

本研究旨在评估罗格列酮(RSG)或吡格列酮(POG)对幼鼠甲状腺功能减退症海马突触可塑性、神经元凋亡、脑源性神经营养因子(BDNF)和一氧化氮(NO)代谢物的影响。动物分为四组:对照组;丙硫氧嘧啶(PTU),饮用水中 0.05%剂量,持续 42 天;PTU-POG;和 PTU-RSG。POG(20mg/kg)和 RSG(4mg/kg)通过 IP 注射给药。我们通过对 Schaffer 侧支通路进行高频刺激,在海马体的角回 1 区进行长时程增强(LTP)。然后,收集海马组织以确定 BDNF 和 NO 水平以及凋亡程度。与对照组相比,PTU 给药降低了 fEPSP 的斜率(10-90%)和幅度。与 PTU 组相比,RSG 或 POG 的注射增加了 PTU-POG 或 PTU-RSG 组的斜率、斜率(10-90%)和 fEPSP 的幅度。PTU 组海马体 TUNEL 阳性神经元和 NO 代谢物的数量高于对照组。RSG 或 POG 增加了 PTU-POG 或 PTU-RSG 组的 BDNF 含量。与 PTU 组相比,POG 或 RSG 处理分别降低了 PTU-POG 或 PTU-RSG 组海马体中的凋亡神经元和 NO 代谢物。本研究结果表明,POG 或 RSG 可使幼鼠甲状腺功能减退症海马体 LTP 损伤、神经元凋亡正常化,并改善海马体组织中的 BDNF 含量。

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