GM1 ganglioside restores dopaminergic neurochemical and morphological markers in aged rats.
The monosialoganglioside GM1 exerts neurotrophic-like activity in vitro and in vivo. In particular, it improves cholinergic neuron morphology and chemistry and learning abilities of cognitively impaired aged rats and young animals with cholinergic lesions, and restores neurochemical, pharmacological, morphological and behavioral parameters in animal models of Parkinson's disease. Our studies present evidence that GM1 reverses dopaminergic deficits in the nigrostriatal neurons of aged rats. GM1 administered to aged Sprague-Dawley rats for 30 days reversed the decreased activity of tyrosine hydroxylase in the midbrain and striatum, elevated the reduced protein content and mRNA levels of the enzyme in the midbrain, and reversed the decrements of dopamine and 3,4-dihydroxyphenylacetic acid content in both the midbrain and striatum. Tyrosine hydroxylase activity of the midbrain, but not of the striatum, remained elevated for 15 days after discontinuing GM1. The count profiles of tyrosine hydroxylase-immunopositive neurons, the size of tyrosine hydroxylase-immunopositive neurons and the number of tyrosine hydroxylase-immunopositive fibers were decreased in the substantia nigra pars compacta and the ventral tegmental area of aged rats. GM1 corrected the morphology of dopaminergic neurons in the substantia nigra pars compacta and partially improved it in the ventral tegmental area. These findings support the notion that the aged striatal dopaminergic neurons respond to GM1, and strengthen the utility of using this compound for combating age-associated neuronal deficits.
Goettl
V M
VM
Department of Pharmacology, The Ohio State University College of Medicine and Public Health, Columbus 43210, USA.
Wemlinger
T A
TA
Duchemin
A M
AM
Neff
N H
NH
Hadjiconstantinou
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D014018:Tissue Distribution / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D005677:G(M1) Ganglioside; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine