Health Sciences Department, State University of Maringá (UEM), Maringá, PR, Brazil.
School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil.
PLoS One. 2021 Apr 15;16(4):e0250079. doi: 10.1371/journal.pone.0250079. eCollection 2021.
The aim of this study was to investigate the effect of rosuvastatin treatment on memory impairment, and anxiogenic-like effects in mice chronically infected with Toxoplasma gondii. For this, Balb/c mice were infected orally with chronic ME-49 strain of Toxoplasma gondii. Oral treatment with rosuvastatin (40mg/kg/day) started on the 51st day post-infection and was performed daily for 21 days. After completion of treatment, anxiety-like effects and locomotion were investigated in the open field (OF) test, whereas novel object recognition (NOR) test was used for evaluation of short- and long-term memory. At the end of the experiments, the brain was collected for Toxoplasma gondii DNA quantification and histopathological analysis. Infection with ME-49 strain decreased the time spent in the center of OF, indicating an anxiogenic effect, without affecting total and peripheral locomotion. Rosuvastatin treatment inhibited the change in the center time. Besides, pharmacological treatment increased total and central locomotion in both non-infected and infected animals. Infection also impaired both short- and long-term memory in the NOR test, and these effects were reverted by rosuvastatin treatment. In addition to effects in behavioral changes, rosuvastatin also reduced parasite load in the brain and attenuated signs of brain inflammation such as perivascular cuffs, inflammatory cell infiltration and tissue damage. These findings indicate for the first time the efficacy of rosuvastatin in treatment of memory impairment and anxiogenic effect evoked by infection with Toxoplasma gondii. These effects might be mediated by reduced cyst load, which in turn decrease inflammation and damage in the brain.
这项研究的目的是调查阿托伐他汀治疗对慢性感染弓形虫的小鼠记忆障碍和焦虑样效应的影响。为此，Balb/c 小鼠经口感染慢性 ME-49 株弓形虫。感染后第 51 天开始口服阿托伐他汀（40mg/kg/天）治疗，每日一次，共 21 天。治疗结束后，在旷场（OF）试验中检测焦虑样效应和运动性，而新物体识别（NOR）试验用于评估短期和长期记忆。实验结束时，采集大脑进行弓形虫 DNA 定量和组织病理学分析。感染 ME-49 株降低了 OF 中心停留时间，表明存在焦虑样效应，而不影响总运动和外周运动。阿托伐他汀治疗抑制了中心时间的变化。此外，药理治疗增加了非感染和感染动物的总运动和中央运动。感染还损害了 NOR 试验中的短期和长期记忆，而阿托伐他汀治疗逆转了这些影响。除了对行为变化的影响外，阿托伐他汀还降低了大脑中的寄生虫负荷，并减轻了血管周围套袖、炎症细胞浸润和组织损伤等脑部炎症的迹象。这些发现首次表明阿托伐他汀在治疗弓形虫感染引起的记忆障碍和焦虑样效应方面的疗效。这些作用可能是通过减少囊泡负荷介导的，从而减少大脑中的炎症和损伤。
