Effects of GM1 ganglioside treatment on pre- and postsynaptic dopaminergic markers in the striatum of parkinsonian monkeys.
GM1 ganglioside administration has previously been shown to increase striatal dopamine levels and to enhance the density of tyrosine hydroxylase-positive fibers in the striatum of monkeys made parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The present study examined the extent to which GM1 administration promotes recovery of dopamine terminals and reverses lesion-induced changes in postsynaptic receptors in the striatum of MPTP-treated monkeys. All MPTP-treated animals developed severe parkinsonism. GM1-treated monkeys exhibited significant functional recovery after 6 weeks of treatment, whereas saline-treated controls remained parkinsonian over the same time period. MPTP exposure resulted in profound decreases in [(3)H]-mazindol binding to dopamine transporters in the caudate and putamen and increased D1 and D2 receptor binding in several striatal regions. GM1 treatment resulted in significant increases in striatal [(3)H]-mazindol binding and decreases in D1 binding compared to control animals in many striatal regions. GM1 treatment did not significantly affect D2 binding. These results show that GM1 treatment can partially restore striatal dopaminergic terminals and partially reverse postsynaptic changes in dopamine receptors in a nonhuman primate model of parkinsonism.
Pope-Coleman
A
A
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Tinker
J P
JP
Schneider
J S
JS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D008454:Mazindol / Q000494:pharmacology; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012453:Saimiri; D013134:Spiperone / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D005677:G(M1) Ganglioside; D013134:Spiperone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008454:Mazindol