Mice deficient in GM1 manifest both motor and non-motor symptoms of Parkinson's disease; successful treatment with synthetic GM1 ganglioside

• Published in: Experimental neurology Vol. 329; p. 113284
• Main Authors: Wu, Gusheng, Lu, Zi-Hua, Seo, Joon Ho, Alselehdar, Samar K., DeFrees, Shawn, Ledeen, Robert W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2020
• Subjects: Animals; Cardiac pathology; Cognitive dysfunction; Disease Models, Animal; Female; G(M1) Ganglioside - administration & dosage; G(M1) Ganglioside - deficiency; G(M1) Ganglioside - genetics; Gastrointestinal Diseases - drug therapy; Gastrointestinal Diseases - genetics; Gastrointestinal Diseases - metabolism; Gastrointestinal symptoms; GM1 ganglioside; Male; Memory Disorders - drug therapy; Memory Disorders - genetics; Memory Disorders - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Motor impairment; Motor Skills Disorders - drug therapy; Motor Skills Disorders - genetics; Motor Skills Disorders - metabolism; N-Acetylgalactosaminyltransferases - deficiency; N-Acetylgalactosaminyltransferases - genetics; Parkinson Disease - drug therapy; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; Cardiac pathology; Parkinson's disease; LP; IHC; aSyn; HT; UPDRS; WT; Cognitive dysfunction; HPLC; HPTLC; PBS; Gastrointestinal symptoms; BSS; DOPAC; pRET; IP; SNpc; Motor impairment; IV; Mab; GM1 ganglioside; GDNF; PD; TH; DA
• ISSN: 0014-4886; 1090-2430; 1090-2430
• DOI: 10.1016/j.expneurol.2020.113284

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. •New mouse model of PD based on GM1 deficiency shows non-movement and movement disorders.•Non-movement disorders include lesions in colon and heart, short-term memory loss.•GM1-deficient mice showed symptoms of constipation characteristic of prodromal PD.•E.coli synthesized GM1 was shown to be effective in remedying all PD lesions.