Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Multi-User Facility, Drug Research and Development Center, Federal University of Ceará, Brazil.
Horm Behav. 2020 Jun;122:104758. doi: 10.1016/j.yhbeh.2020.104758. Epub 2020 Apr 28.
Cognitive impairment is identified as one of the diagnostic criteria for major depressive disorder and can extensively affect the quality of life of patients. Based on these findings, this study aimed to investigate the possible effects of Riparin IV (Rip IV) on cognitive impairment induced by chronic administration of corticosterone in mice.
Female Swiss mice were divided into four groups: control (Control), corticosterone (Cort), Riparin IV (Cort + Rip IV), and Fluvoxamine (Cort + Flu). Three groups were administered corticosterone (20 mg/kg) subcutaneously during the 22-day study, while the control group received only vehicle. After the 14th day, the groups were administered medications: Riparin IV (Rip IV), fluvoxamine (Flu), or distilled water, by gavage, 1 h after the subcutaneous injections. After treatment, mice underwent behavioral testing, and brain areas were removed for oxidative stress and cytokine content assays.
The results revealed that Cort-treated mice developed a cognitive impairment and exhibited a neuroinflammatory profile with an oxidative load and Th1/Th2 cytokine imbalance. Rip IV treatment significantly ameliorated the cognitive deficit induced by Cort and displayed a neuroprotective effect.
The antidepressant-like ability of Rip IV treatment against chronic Cort-induced stress may be due to its potential to mitigate inflammatory damage and oxidative stress. The antioxidant and anti-inflammatory effect observed indicates Rip IV as a possible drug for antidepressant treatment of non-responsive patients with severe and cognitive symptoms.
认知障碍被确定为重度抑郁症的诊断标准之一，可广泛影响患者的生活质量。基于这些发现，本研究旨在探讨瑞巴派特 IV（Rip IV）对慢性给予皮质酮诱导的小鼠认知障碍的可能影响。
雌性瑞士小鼠分为四组：对照组（Control）、皮质酮组（Cort）、瑞巴派特 IV 组（Cort+Rip IV）和氟伏沙明组（Cort+Flu）。三组在 22 天的研究期间接受皮质酮（20mg/kg）皮下注射，而对照组仅接受载体。第 14 天，各组给予药物：瑞巴派特 IV（Rip IV）、氟伏沙明（Flu）或灌胃蒸馏水，皮下注射后 1 小时。治疗后，小鼠进行行为测试，并取出脑区进行氧化应激和细胞因子含量测定。
结果表明，皮质酮处理的小鼠出现认知障碍，并表现出神经炎症特征，伴有氧化负荷和 Th1/Th2 细胞因子失衡。瑞巴派特 IV 治疗显著改善了皮质酮诱导的认知缺陷，并表现出神经保护作用。
瑞巴派特 IV 治疗慢性皮质酮诱导应激的抗抑郁样作用可能与其减轻炎症损伤和氧化应激的潜力有关。观察到的抗氧化和抗炎作用表明瑞巴派特 IV 可能是治疗无反应、伴有严重和认知症状的患者的抗抑郁药物。
