The present study was designed to evaluate the role of cAMP-PKA-CREB signaling in mediating the neuroprotective effects of curcumin against DCAA-induced oxidative stress, inflammation and impaired synaptic plasticity in rats. Sixty Sprague-Dawley rats were randomly divided into five groups, and we assessed the histomorphological, behavioral and biochemical characteristics to investigate the beneficial effects of different concentrations of curcumin against DCAA-induced neurotoxicity in rat hippocampus. The results indicated that animal weight gain and food consumption were not significantly affected by DCAA. However, behavioral tests, including morris water maze and shuttle box, showed varying degrees of alterations. Additionally, we found significant changes in hippocampal neurons by histomorphological observation. DCAA exposure could increase lipid peroxidation, reactive oxygen species (ROS), inflammation factors while reducing superoxide dismutase (SOD) activity and glutathione (GSH) level accompanied by DNA damage in the hippocampus. Furthermore, we found that DCAA exposure could cause a differential modulation of mRNA and proteins (cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95), synaptophysin (SYP)). Conversely, various doses of curcumin attenuated DCAA-induced oxidative stress, inflammation response and impaired synaptic plasticity, while elevating cAMP, PKA, p-CREB, BDNF, PSD-95, SYP levels. Thus, curcumin could activate the cAMP-PKA-CREB signaling pathway, conferring neuroprotection against DCAA-induced neurotoxicity.

本研究旨在评估 cAMP-PKA-CREB ​​信号传导在介导姜黄素对 DCAA 诱导的大鼠氧化应激、炎症和突触可塑性受损的神经保护作用中的作用。60 只 Sprague-Dawley 大鼠随机分为五组，我们评估了组织形态学、行为学和生化特征，以研究不同浓度的姜黄素对 DCAA 诱导的大鼠海马神经毒性的有益作用。结果表明DCAA对动物体重增加和食物消耗没有显着影响。然而，行为测试，包括莫里斯水迷宫和穿梭箱，显示出不同程度的改变。此外，我们通过组织形态学观察发现了海马神经元的显着变化。DCAA 暴露会增加脂质过氧化、活性氧 (ROS)、炎症因子，同时降低超氧化物歧化酶 (SOD) 活性和谷胱甘肽 (GSH) 水平，同时伴有海马中的 DNA 损伤。此外，我们发现 DCAA 暴露可能导致 mRNA 和蛋白质（环磷酸腺苷 (cAMP)、蛋白激酶 A (PKA)、cAMP 反应元件结合蛋白 (CREB)、p-CREB、脑源性神经营养因子 (BDNF)、突触后密度-95 (PSD-95)、突触素 (SYP))。相反，不同剂量的姜黄素可减弱 DCAA 诱导的氧化应激、炎症反应和突触可塑性受损，同时提高 cAMP、PKA、p-CREB、BDNF、PSD-95、SYP 水平。因此，姜黄素可以激活 cAMP-PKA-CREB ​​信号通路，