PDF(Pubmed)
Abstract：
BACKGROUND: Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical.
METHODS: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice\'s energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration.
RESULTS: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex.
CONCLUSIONS: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.
METHODS: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice\'s energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration.
RESULTS: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex.
CONCLUSIONS: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.
摘要：
背景：人类或小鼠感染广州管圆线虫（AC）可导致严重的嗜酸性粒细胞性脑膜炎或脑炎，导致各种神经损伤。开发有效的神经保护药物以改善受影响个体的生活质量至关重要。
方法：我们对AC感染小鼠大脑中的微阵列基因表达（GSE159486）进行了基因本体富集分析。通过实时定量PCR(RT-qPCR)和免疫荧光检测黑色素浓集激素(MCH)的表达水平。使用间接量热法评估代谢参数，和小鼠的能量代谢通过病理性苏木精和伊红（H&E）染色评估，血清生化测定，和免疫组织化学。行为测试评估认知和运动功能。使用蛋白质印迹法测量突触相关蛋白的表达。小鼠经鼻给药补充MCH。
结果：感染后，观察到Pmch表达和编码的MCH显著降低。感染小鼠表现出明显的体重减轻，大量食用糖和白色脂肪组织，减少移动距离,速度降低，与对照组相比。值得注意的是,MCH的鼻腔给药对抗AC感染引起的能量失衡和运动障碍，提高生存率。MCH治疗还增加了突触后密度蛋白95（PSD95）和微管相关蛋白2（MAP2）的表达水平，以及上调皮质B细胞白血病/淋巴瘤2（Bcl2）的转录水平。
结论：我们的研究结果表明，MCH通过减少突触蛋白的丢失来改善运动障碍，表明其作为治疗AC感染的潜力。
方法：我们对AC感染小鼠大脑中的微阵列基因表达（GSE159486）进行了基因本体富集分析。通过实时定量PCR(RT-qPCR)和免疫荧光检测黑色素浓集激素(MCH)的表达水平。使用间接量热法评估代谢参数，和小鼠的能量代谢通过病理性苏木精和伊红（H&E）染色评估，血清生化测定，和免疫组织化学。行为测试评估认知和运动功能。使用蛋白质印迹法测量突触相关蛋白的表达。小鼠经鼻给药补充MCH。
结果：感染后，观察到Pmch表达和编码的MCH显著降低。感染小鼠表现出明显的体重减轻，大量食用糖和白色脂肪组织，减少移动距离,速度降低，与对照组相比。值得注意的是,MCH的鼻腔给药对抗AC感染引起的能量失衡和运动障碍，提高生存率。MCH治疗还增加了突触后密度蛋白95（PSD95）和微管相关蛋白2（MAP2）的表达水平，以及上调皮质B细胞白血病/淋巴瘤2（Bcl2）的转录水平。
结论：我们的研究结果表明，MCH通过减少突触蛋白的丢失来改善运动障碍，表明其作为治疗AC感染的潜力。
