The isoquinoline 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) has been studied due to its multitarget properties, such as modulation of GABAergic and glutamatergic systems, antioxidant, and anti-inflammatory. This study investigated the contribution of oxidative stress, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase (HO-1) signaling, and the cholinergic system to the anti-amnesic action of FDPI in mice. Adult male Swiss mice received FDPI for 5 days (5-25 mg/kg, i.g.); the animals received scopolamine (1 mg/kg, i.p) from day 3-5. The vehicle-control group was carried out. Afterward, mice performed object recognition tests (ORTs). Scopolamine induced amnesia and cholinergic dysfunction by increasing the acetylcholinesterase (AChE) activity and content, decreasing the muscarinic M1 receptor levels in the prefrontal cortex and hippocampus of mice. This study reveals that scopolamine altered oxidative stress parameters differently in the prefrontal cortex and hippocampus of mice. Whereas the prefrontal cortex was susceptible to oxidative stress, none of the parameters evaluated was altered in the hippocampus of scopolamine-treated mice. FDPI at doses of 10 and 25 mg/kg had an anti-amnesic effect in the ORT tests. FDPI 10 mg/kg reversed the increase in the AChE activity and content, oxidative stress parameters, and modulated Nrf2/HO-1 signaling in the prefrontal cortex of scopolamine-exposed mice. Pearson's correlation analyses reinforced the contribution of the prefrontal cortical cholinergic system, oxidative stress as well as Nrf2/HO-1 signaling in the anti-amnesic effect of FDPI. Considering FDPI effects on the hippocampus, it was effective against the cholinergic dysfunction, AChE activity and content, and M1 receptor levels, which collectively could contribute to its anti-amnesic effect.

中文翻译：

---

胆碱能系统和Nrf2 / HO-1信号对小鼠7-氟-1,3-二苯基异喹啉-1-胺的抗记忆功能的贡献。

异喹啉7-氟-1,3-二苯基异喹啉-1-胺（FDPI）由于具有多靶点性质而受到研究，例如调节GABA能和谷氨酸能系统，抗氧化剂和抗炎作用。这项研究调查了氧化应激，核因子（类胡萝卜素衍生的2）样2（Nrf2）/血红素加氧酶（HO-1）信号转导和胆碱能系统对FDPI在小鼠中的抗健忘作用的贡献。成年雄性瑞士小鼠接受FDPI 5天（5-25 mg / kg，ig）; 从第3-5天开始，动物接受东pol碱（1 mg / kg，ip）。进行了车辆对照组。之后，小鼠进行了对象识别测试（ORT）。东co碱可通过增加乙酰胆碱酯酶（AChE）的活性和含量来诱发健忘症和胆碱能功能障碍，降低小鼠前额叶皮层和海马中毒蕈碱M1受体的水平。这项研究表明东pol碱在小鼠的前额叶皮层和海马中改变了氧化应激参数。尽管前额叶皮层容易受到氧化应激，但东sco碱治疗的小鼠海马中所评估的参数均未改变。FDPI的剂量为10和25 mg / kg，在ORT测试中具有抗遗忘作用。FDPI 10 mg / kg逆转了暴露于东mice碱的小鼠前额叶皮层中AChE活性和含量，氧化应激参数以及Nrf2 / HO-1信号转导的增加。Pearson的相关分析加强了前额叶皮层胆碱能系统，氧化应激以及Nrf2 / HO-1信号在FDPI的抗记忆删除中的作用。