Mild cognitive impairment in Parkinson's disease (PD-MCI) is considered as a nonmotor clinical symptom in Parkinson’s disease (PD). Microglia-mediated inflammation contributes to cognitive function impairment. Poloxamer 188 (P188) is an amphipathic polymer which has cytoprotective effect in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced dopaminergic (DA) neurons degeneration in PD. But whether P188 could ameliorate cognitive impairment in PD is still illusive. In the present study, we showed in a mouse model that paraquat (10 mg/kg) and maneb (30 mg/kg) (P + M) treatment intraperitoneally twice a week for 6 consecutive weeks resulted in cognitive deficits and synapse loss in hippocampus, together with DA neuron damage in the substantia nigra pars compacta (SNpc). P188 (0.8 g/kg) injection via tail vein 30 min after P + M administration significantly restored DA neuron numbers in SNpc and synapse density in hippocampus, and alleviated P + M-mediated cognitive function impairment in novel object recognition task and morris water maze task (MWM). Pathological synapse loss might be attributed to increased microglial phagocytic activity and cell density, and P188 prevented P + M-induced phagocytic state changes of microglia, such as increase in cell body size and decrease in process length, and upregulated microglia abundance in hippocampus. Consistently, P188 attenuated P + M-mediated increased mRNA levels of microglia proliferation related CSF1r and CSF2ra, microglial engulfment associated CD68, ICAM1, and ICAM2, and pro-inflammatory IL-6, IL-1β, CD11b, and TNF-α in hippocampus. Together, these findings suggest that the biocompatible polymer P188 blunts microglia activation which may promote synaptic loss and exacerbate cognitive function in a mouse model of PD-MCI.

帕金森氏病（PD-MCI）的轻度认知障碍被认为是帕金森氏病（PD）的非运动性临床症状。小胶质细胞介导的炎症导致认知功能受损。泊洛沙姆188（P188）是两亲性聚合物，在1-甲基-4-苯基-1、2、3、6-四氢吡啶（MPTP）诱导的PD多巴胺能（DA）神经元变性中具有细胞保护作用。但是P188是否可以减轻PD的认知障碍仍然是一个未知数。在本研究中，我们在小鼠模型中显示，百草枯（10 mg / kg）和maneb（30 mg / kg）（P + M）每周两次腹膜内治疗，连续6周导致海马认知障碍和突触丧失，以及黑质致密部（SNpc）中的DA神经元损伤。P188（0。P + M给药后30分钟通过尾静脉注射8 g / kg）可显着恢复SNpc中DA神经元数量和海马突触密度，并减轻P + M介导的新型物体识别任务和morris water maze任务的认知功能障碍（ MWM）。病理性突触丧失可能归因于小胶质细胞吞噬活性和细胞密度的增加，而P188阻止了P + M诱导的小胶质细胞的吞噬状态变化，例如细胞体大小的增加和过程长度的减少，以及海马小胶质细胞丰度的上调。一致地，P188减弱了P + M介导的小胶质细胞增殖相关的CSF1r和CSF2ra，小胶质细胞吞噬相关的CD68，ICAM1和ICAM2以及海马中促炎性IL-6，IL-1β，CD11b和TNF-α的mRNA水平升高。 。一起，