GM1 ganglioside potentiates the effect of nerve growth factor in preventing vinblastine-induced sympathectomy in newborn rats.
The effects of vinblastine (VNB) and nerve growth factor (NGF) administrations were assessed on sympathetic nerve terminals by measuring the noradrenaline (NA) content in the heart, spleen and kidneys of developing animals. Six-day-old rats, treated with 0.15 mg/kg VNB on postnatal day 3 (P3) showed a dramatic decrease of NA content in all these organs. This reduction was prevented by daily administrations of NGF on P3, P4 and P5. The effectiveness of NGF in inhibiting the VNB-induced sympathectomy was related to the dose administered and to the time interval between the VNB administration and the first NGF injection given on P3. Dose-response curves to NGF (ranging from 0.01 to 0.5 mg/kg) were obtained in both heart and spleen of VNB-treated animals. Thus, this experimental paradigm provides a quantitative assessment of the NGF activity in vivo. The systemic administration of GM1 (30 mg/kg) on P3, P4 and P5, was able to potentiate the NGF activity in preventing the VNB-induced sympathectomy. This GM1 effect was more evident in the heart and may be, at least in part, attributed to increased NGF prevention of neuronal cell death due to VNB. These results suggest an in vivo interaction between exogenous GM1 and NGF and are consistent with the view that neuronal cell repair related to in vivo administration of this ganglioside may rely on its capability to modulate the activity of endogenously occurring neuronotrophic factors.
Vantini
G
G
Fidia Research Laboratories, Abano Terme, Italy.
Fusco
M
M
Bigon
E
E
Leon
A
A
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000294:innervation; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000187:drug effects / Q000294:innervation; D013563:Sympathectomy, Chemical; D014747:Vinblastine / Q000494:pharmacology*
D009414:Nerve Growth Factors; D005677:G(M1) Ganglioside; D014747:Vinblastine; D009638:Norepinephrine