Mihaylova Anita, Doncheva Nina, Zlatanova Hristina, Delev Delian, Ivanovska Mariya, Koeva Yvetta, Murdjeva Marianna, Kostadinov Ilia
Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University of Plovdiv, Bulgaria.
Department of Pharmacology and Clinical Pharmacology, Medical Faculty, Medical University of Plovdiv, Bulgaria.
Iran J Basic Med Sci. 2021 May;24(5):577-585. doi: 10.22038/ijbms.2021.50439.11488.
A variety of cytokines are involved in cognitive functioning. Balance restoration between protective and degenerative neuro-inflammation is of great interest in newer therapeutic approaches. In the current study, we investigated the effect of pramipexole (PMX) on memory functions, hippocampal amyloid deposition, serum cytokines, and brain-derived neurotrophic factor (BDNF) levels in lipopolysaccharide (LPS) challenged-rats.
Male Wistar rats were divided into 5 groups (n=8): control (saline), lipoppolysacharide (LPS 250 mcg/kg bw), and experimental groups (LPS and PMX 0.5, 1, and 3 mg/kg bw). Learning and memory were assessed by the novel object recognition test (NORT), Y-maze, and step-through test. Immunological and histological assays were performed.
In memory tasks, LPS-challenged rats showed reduction in the observed parameters. In NORT, PMX 1 mg/kg increased recognition index compared with controls, whereas the other two doses increased this index only against the LPS-control. In Y-maze, all doses of PMX significantly had increased alternation when compared with LPS. In the step-through test, only the lowest dose of PMX extended the latency compared with LPS. Histological examination revealed that PMX at doses of 0.5 and 1 mg/kg reduced amyloid deposition in the hippocampus. Interleukin (IL)-10 serum levels were elevated by 1 mg/kg PMX. Tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 serum levels remained under the detectable minimum in all experimental groups. PMX at all doses significantly decreased BDNF serum concentration.
In rats with LPS-induced neuro-inflammation PMX improved hippocampal-dependent memory and exerted immuno-modulatory effects by increasing IL-10.
多种细胞因子参与认知功能。在新的治疗方法中,恢复保护性和退行性神经炎症之间的平衡备受关注。在本研究中,我们调查了普拉克索(PMX)对脂多糖(LPS)攻击的大鼠的记忆功能、海马淀粉样蛋白沉积、血清细胞因子和脑源性神经营养因子(BDNF)水平的影响。
雄性Wistar大鼠分为5组(n = 8):对照组(生理盐水)、脂多糖组(LPS 250 mcg/kg体重)和实验组(LPS与PMX 0.5、1和3 mg/kg体重)。通过新物体识别测试(NORT)、Y迷宫和穿梭试验评估学习和记忆。进行免疫和组织学检测。
在记忆任务中,LPS攻击的大鼠观察参数降低。在NORT中,与对照组相比,PMX 1 mg/kg增加了识别指数,而其他两个剂量仅相对于LPS对照组增加了该指数。在Y迷宫中,与LPS相比,所有剂量的PMX均显著增加了交替率。在穿梭试验中,与LPS相比,只有最低剂量的PMX延长了潜伏期。组织学检查显示,0.5和1 mg/kg剂量的PMX减少了海马中的淀粉样蛋白沉积。1 mg/kg PMX使白细胞介素(IL)-10血清水平升高。在所有实验组中,肿瘤坏死因子(TNF)-α和转化生长因子(TGF)-β1血清水平均低于可检测的最小值。所有剂量的PMX均显著降低BDNF血清浓度。
在LPS诱导神经炎症的大鼠中,PMX改善了海马依赖性记忆,并通过增加IL-10发挥免疫调节作用。