Manganese (Mn) is an essential metallic trace element involved in several vital biological functions. Conversely, exposure to excessive levels of Mn induces manganism, causing neurodegeneration and symptoms similar to those seen in Parkinson's disease (PD). Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid exhibiting neuroprotective properties against neurodegenerative diseases and brain injuries and is known to easily incorporate into membrane phospholipids of brain cells and meditates its corrective actions. In the present study, mice were used for a sub-acute Mn intoxication model to investigate DHA neuroprotective potential against Mn neurotoxicity. We also seek to understand the mechanism by which Mn intoxication induces these motor impairments at 30 mg/kg, by pretreatment with DHA at 200 mg/kg and assessment of changes in spontaneous locomotor behavior by open field test (OF), motor coordination using the rotarod test (RR) and strength by mean of weights test (WT). To highlight these effects on brain neurotransmission, we evaluated the tyrosine hydroxylase immunoreactivity (TH-IR) within substantia nigra compacta (SNC) and striatum (St). Results showed that Mn intoxication significantly altered motor behavior parameters including, decreased of traveled distance by 46%, decreased mean speed by 36%, reduced the ability to sustain the rotarod test to 42%; Moreover, a drop score was obtained using weights test and reflecting affected strength in Mn-intoxicated animals. Pretreatment by DHA prevents mice from Mn toxicity and maintain normal spontaneous activity, motor coordination and strength. Data also showed the ability of Mn to disrupt dopamine neurotransmission by altering tyrosine hydroxylase activity in the nigrostriatal pathway while in pretreated animals, DHA prevented this disruption. Data approved the potential neurotoxic effect of Mn as a risk factor of the Parkinsonism onset, and then demonstrated for the first time the neuroprotective and nutraceutical outcomes of DHA in the sub-acute Mn-intoxication animal model.

中文翻译：

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二十二碳六烯酸对亚急性锰中毒诱导的小鼠多巴胺能和运动障碍的神经保护作用

锰 (Mn) 是一种必需的金属微量元素，涉及多种重要的生物功能。相反，接触过量的锰会诱发锰中毒，导致神经变性和类似于帕金森病 (PD) 的症状。二十二碳六烯酸 (DHA) 是一种长链多不饱和脂肪酸，对神经退行性疾病和脑损伤具有神经保护作用，众所周知，它很容易结合到脑细胞的膜磷脂中并发挥其纠正作用。在本研究中，小鼠被用于亚急性锰中毒模型，以研究 DHA 对锰神经毒性的神经保护潜力。我们还试图了解 Mn 中毒在 30 mg/kg 时诱导这些运动障碍的机制，通过用 200 mg/kg 的 DHA 预处理并通过开放场测试 (OF)、使用旋转棒测试 (RR) 的运动协调和通过重量测试 (WT) 的力量评估自发运动行为的变化。为了强调这些对脑神经传递的影响，我们评估了黑质致密体 (SNC) 和纹状体 (St) 内的酪氨酸羟化酶免疫反应性 (TH-IR)。结果表明，锰中毒显着改变了运动行为参数，包括行驶距离减少 46%，平均速度降低 36%，维持旋转棒测试的能力降低至 42%；此外，使用体重测试获得了下降分数，并反映了锰中毒动物的受影响强度。DHA 预处理可防止小鼠遭受锰中毒并维持正常的自发活动、运动协调性和力量。数据还显示 Mn 通过改变黑质纹状体通路中的酪氨酸羟化酶活性来破坏多巴胺神经传递的能力，而在预处理的动物中，DHA 阻止了这种破坏。数据证实锰的潜在神经毒性作用是帕金森病发作的危险因素，然后首次在亚急性锰中毒动物模型中证明了 DHA 的神经保护和营养作用。