Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b Street, 20-090 Lublin, Poland.
Int J Mol Sci. 2022 May 14;23(10):5502. doi: 10.3390/ijms23105502.
Many relevant studies, as well as clinical practice, confirm that untreated diabetes predisposes the development of neuroinflammation and cognitive impairment. Having regard for the fact that PPAR are widely distributed in the brain and PPAR ligands may regulate the inflammatory process, the anti-inflammatory potential of the PPAR agonist, pioglitazone, was assessed in a mouse model of neuroinflammation related with diabetes. In this regard, the biochemical and molecular indicators of neuroinflammation were determined in the hippocampus and prefrontal cortex of diabetes mice. The levels of cytokines (IL-1, IL-6, and TNF) and the expression of genes ( and ) were measured. In addition, behavioral tests such as the open field test, the hole-board test, and the novel object recognition test were conducted. A 14-day treatment with pioglitazone significantly decreased IL-6 and TNFα levels in the prefrontal cortex and led to the downregulation of expression and the upregulation of expression in both brain regions of diabetic mice. Pioglitazone, by targeting neuroinflammatory signaling, improved memory and exploratory activity in behavioral tests. The present study provided a potential theoretical basis and therapeutic target for the treatment of neuroinflammation associated with diabetes. Pioglitazone may provide a promising therapeutic strategy in diabetes patients with muffled of behavioral activity.
许多相关研究以及临床实践证实，未经治疗的糖尿病会增加神经炎症和认知障碍的风险。鉴于 PPAR 广泛分布于大脑中，并且 PPAR 配体可能调节炎症过程，因此评估了 PPAR 激动剂吡格列酮在与糖尿病相关的神经炎症的小鼠模型中的抗炎潜力。为此，测定了糖尿病小鼠海马体和前额叶皮层的神经炎症的生化和分子指标。测定了细胞因子（IL-1、IL-6 和 TNF）的水平和基因（和）的表达。此外，还进行了行为测试，如旷场试验、洞板试验和新物体识别试验。吡格列酮治疗 14 天可显著降低前额叶皮层中的 IL-6 和 TNFα 水平，并导致糖尿病小鼠两个脑区的 表达下调和 表达上调。吡格列酮通过靶向神经炎症信号通路，改善了行为测试中的记忆和探索活动。本研究为治疗与糖尿病相关的神经炎症提供了潜在的理论依据和治疗靶点。吡格列酮可能为行为活动减弱的糖尿病患者提供一种有前景的治疗策略。
