Department of Physiology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.
Department of Biology, Faculty of Science, Erciyes University, Kayseri, Türkiye.
Behav Brain Res. 2023 Aug 24;452:114565. doi: 10.1016/j.bbr.2023.114565. Epub 2023 Jul 5.
It is well established that rats exposed to inflammation during pregnancy or the perinatal period have an increased chance of developing schizophrenia-like symptoms and behaviors, and people with schizophrenia also have raised levels of inflammatory markers. Therefore, there is evidence supporting the idea that anti-inflammatory drugs may have therapeutic benefits. Aceclofenac is a nonsteroidal anti-inflammatory drug that has anti-inflammatory properties and is used clinically to treat inflammatory and painful processes such as osteoarthritis and rheumatoid arthritis, making it a potential candidate for preventive or adjunctive therapy in schizophrenia. This study therefore examined the effect of aceclofenac in a maternal immune activation model of schizophrenia, in which polyinosinic-polycytidylic acid (Poly I:C) (8 mg/kg, i.p.) was administered to pregnant rat dams. Young female rat pups received daily aceclofenac (5, 10, and 20 mg/kg, i.p., n = 10) between postnatal day 56 and 76. The effects of aceclofenac were compared with assessment of behavioral tests and ELISA results. During the postnatal days (PNDs) 73-76, behavioral tests were conducted in rats, and on PND 76, ELISA tests were performed to examine the changes in Tumor necrosis factor alpha (TNF-α), Interleukin-1β (IL-1β), Brain-derived neurotrophic factor (BDNF), and nestin levels. Aceclofenac treatment reversed deficits in prepulse inhibition, novel object recognition, social interaction, and locomotor activity tests. In addition, aceclofenac administration decreased TNF-α and IL-1β expression in the prefrontal cortex and hippocampus. In contrast, BDNF and nestin levels did not change significantly during treatment with aceclofenac. Taken together, these results suggest that aceclofenac may be an alternative therapeutic adjunctive strategy to improve the clinical expression of schizophrenia in the further studies.
众所周知，在怀孕期间或围产期暴露于炎症的大鼠有发展出类似精神分裂症的症状和行为的机会增加，并且精神分裂症患者也有升高的炎症标志物水平。因此，有证据支持这样一种观点，即抗炎药可能具有治疗益处。醋氯芬酸是一种非甾体抗炎药，具有抗炎特性，临床上用于治疗炎症和疼痛过程，如骨关节炎和类风湿关节炎，使其成为精神分裂症预防或辅助治疗的潜在候选药物。因此，本研究在精神分裂症的母体免疫激活模型中检查了醋氯芬酸的作用，其中聚肌苷酸-聚胞苷酸（Poly I:C）（8mg/kg，ip）给予怀孕的大鼠母体。年轻的雌性幼鼠在产后第 56 天至 76 天之间每天接受醋氯芬酸（5、10 和 20mg/kg，ip，n=10）。将醋氯芬酸的作用与行为测试和 ELISA 结果的评估进行了比较。在产后第 73-76 天期间对大鼠进行行为测试，在产后第 76 天进行 ELISA 测试，以检查肿瘤坏死因子 alpha（TNF-α）、白细胞介素-1β（IL-1β）、脑源性神经营养因子（BDNF）和巢蛋白水平的变化。醋氯芬酸治疗逆转了条件性回避反射、新物体识别、社会互动和运动活性测试中的缺陷。此外，醋氯芬酸给药降低了前额叶皮层和海马体中 TNF-α和 IL-1β的表达。相比之下，在醋氯芬酸治疗期间 BDNF 和巢蛋白水平没有明显变化。总之，这些结果表明，醋氯芬酸可能是改善进一步研究中精神分裂症临床表达的替代治疗辅助策略。
