title: GM1 ganglioside treatment partially reverses the nigrostriatal dopamine defect in the weaver mutant mouse.
abstract: The weaver mutation in the mouse is a developmental disorder characterized by cerebellar atrophy as well as decreased numbers of substantia nigra dopaminergic neurons and a striatal dopamine loss. Since the nigrostriatal dopamine loss occurs postnatally, the present study was performed to determine whether early intervention with GM1 ganglioside could alter the extent of this dopamine loss. Weaver mice that received injections of GM1 ganglioside (30 mg/kg) daily, beginning at 7-10 days of age, had significantly higher striatal dopamine levels and significantly more tyrosine hydroxylase-positive substantia nigra pars compacta neurons than weaver mice that received only daily saline injections. These results show that GM1 treatment can alter at least some aspects of this inherited developmental disorder. If the weaver defect is related to a deprivation of trophic support for certain midbrain dopaminergic neurons, the presence of GM1 may be able to enhance the survival of these neurons.
authors.affiliation: Department of Neurology, Hahnemann University, Philadelphia, PA 19102.
authors.forename: J S
authors.initials: JS
authors.lastname: Schneider
authors.forename: M G
authors.initials: MG
authors.lastname: Smith
authors.forename: L
authors.initials: L
authors.lastname: DiStefano
authors.forename: J
authors.initials: J
authors.lastname: Berrian
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008818:Mice, Neurologic Mutants; D017072:Neostriatum / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000201:enzymology; D013378:Substantia Nigra / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; D005677:G(M1) Ganglioside; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine