Mice deficient in GM1 manifest both motor and non-motor symptoms of Parkinson's disease; successful treatment with synthetic GM1 ganglioside
| Autor: | Joon Ho Seo, Gusheng Wu, Zi-Hua Lu, Shawn DeFrees, Samar K. Alselehdar, Robert W. Ledeen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Parkinson's disease Cognitive systems Gastrointestinal Diseases Cardiac pathology Mice Transgenic Disease G(M1) Ganglioside 03 medical and health sciences Mice 0302 clinical medicine Developmental Neuroscience Internal medicine medicine Animals Mice Knockout Memory Disorders business.industry Parkinson Disease Transfection medicine.disease Gm1 ganglioside Mice Inbred C57BL Motor Skills Disorders Disease Models Animal 030104 developmental biology Endocrinology Neurology B4GALNT1 Gene Non motor N-Acetylgalactosaminyltransferases Female business 030217 neurology & neurosurgery |
| Zdroj: | Experimental neurology. 329 |
| ISSN: | 1090-2430 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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