GM1 enhances dopaminergic markers in the brain of aged rats.
A number of presynaptic markers are compromised in the dopaminergic neurons of aged Sprague-Dawley rats (22 months old) compared with young rats (3 months old). Indeed, in the striatum of the aged rats there is a diminished capacity to transport dopamine (DA), to bind the dopamine transporter (DAT) marker mazindol, to bind the vesicular monoamine transporter 2 (VMAT2) marker dihydrotetrabenazine, and to release DA under basal conditions or after induction by K(+) or amphetamine. Furthermore, the expression of DAT and VMAT2 mRNA in the midbrain is suppressed. GM1 ganglioside, 30 mg/kg ip daily, administered for 30 days, restores the afore-mentioned markers to values approaching those for young rats. Taken together with our published observations that GM1 partially restores tyrosine hydroxylase activity and DA metabolism in aged nigrostriatal and mesoaccumbal neurons and improves their morphology, our work suggests that GM1 might act as a dopaminergic neurotrophic factor in the aged brain and be a useful adjuvant for treating age-associated dopaminergic deficits.
Goettl
V M
VM
Department of Pharmacology, College of Medicine and Public Health, Ohio State University, Columbus, OH 43210, USA.
Zhang
H
H
Burrows
A C
AC
Wemlinger
T A
TA
Neff
N H
NH
Hadjiconstantinou
M
M
D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011188:Potassium / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; C493454:Slc18a2 protein, rat; C493216:Slc6a3 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D005677:G(M1) Ganglioside; D000661:Amphetamine; D011188:Potassium; D004298:Dopamine