Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, United States.
Seneb BioSciences, Inc., United States.
Exp Neurol. 2020 Jul;329:113284. doi: 10.1016/j.expneurol.2020.113284. Epub 2020 Mar 9.
Parkinson's disease (PD) is a major neurodegenerative disorder characterized by a variety of non-motor symptoms in addition to the well-recognized motor dysfunctions that have commanded primary interest. We previously described a new PD mouse model based on heterozygous disruption of the B4galnt1 gene leading to partial deficiency of the GM1 family of gangliosides that manifested several nigrostriatal neuropathological features of PD as well as movement impairment. We now show this mouse also suffers three non-motor symptoms characteristic of PD involving the gastrointestinal, sympathetic cardiac, and cerebral cognitive systems. Treatment of these animals with a synthetic form of GM1 ganglioside, produced by transfected E. coli, proved ameliorative of these symptoms as well as the motor defect. These findings further suggest subnormal GM1 to be a systemic defect constituting a major risk factor in sporadic PD and indicate the B4galnt1(+/-) (HT) mouse to be a true neuropathological model that recapitulates both motor and non-motor lesions of this condition.
帕金森病（PD）是一种主要的神经退行性疾病，除了广为人知的运动功能障碍外，还伴有多种非运动症状，这些症状引起了主要关注。我们之前描述了一种新的 PD 小鼠模型，该模型基于 B4galnt1 基因的杂合缺失，导致 GM1 神经节苷脂家族的部分缺失，表现出几种 PD 的黑质纹状体神经病理学特征以及运动障碍。我们现在还发现这种小鼠还患有三种非运动症状，涉及胃肠道、交感心脏和大脑认知系统。用通过转染大肠杆菌产生的 GM1 神经节苷脂的合成形式对这些动物进行治疗，证明可改善这些症状以及运动缺陷。这些发现进一步表明，GM1 功能低下是散发性 PD 的系统性缺陷，是一个主要的危险因素，并表明 B4galnt1(+/-)（HT）小鼠是一种真正的神经病理学模型，可再现该疾病的运动和非运动损伤。
