GM1 ganglioside treatment protects against long-term neurotoxic effects of neonatal X-irradiation on cerebellar cortex cytoarchitecture and motor function.
Exposure of neonatal rats to a 5 Gy dose of X-irradiation induces permanent abnormalities in cerebellar cortex cytoarchitecture (disarrangement of Purkinje cells, reduction of thickness of granular cortex) and neurochemistry (late increase in noradrenaline levels), and motor function (ataxic gait). The neuroprotective effects of gangliosides have been demonstrated using a variety of CNS injuries, including mechanical, electrolytic, neurotoxic, ischemic, and surgical lesions. Here, we evaluated whether systemically administered GM1 ganglioside protects against the long-term CNS abnormalities induced by a single exposure to ionizing radiation in the early post-natal period. Thus, neonatal rats were exposed to 5 Gy X-irradiation, and subcutaneously injected with one dose (30 mg/kg weight) of GM1 on h after exposure followed by three daily doses. Both at post-natal days 30 and 90, gait and cerebellar cytoarchitecture in X-irradiated rats were significantly impaired when compared to age-matched controls. By contrast, both at post-natal days 30 and 90, gait in X-irradiated rats that were treated with GM1 was not significantly different from that in non-irradiated animals. Furthermore, at post-natal day 90, cerebellar cytoarchitecture was still well preserved in GM1-treated, X-irradiated animals. GM1 failed to modify the radiation-induced increase in cerebellar noradrenaline levels. Present data indicate that exogenous GM1, repeatedly administered after neonatal X-irradiation, produces a long-term radioprotection, demonstrated at both cytoarchitectural and motor levels.
Guelman
L R
LR
1a Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 piso 15, 1121, Buenos Aires, Argentina. lguelman@fmed.uba.ar
Zorrilla Zubilete
M A
MA
Ríos
H
H
Dopico
A M
AM
Zieher
L M
LM
D000818:Animals; D000831:Animals, Newborn; D002525:Cerebellar Cortex / Q000473:pathology* / Q000503:physiopathology / Q000528:radiation effects; D005121:Extremities / Q000502:physiology; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005684:Gait / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000737:chemistry / Q000473:pathology / Q000528:radiation effects*; D009638:Norepinephrine / Q000032:analysis; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D011837:Radiation-Protective Agents; D005677:G(M1) Ganglioside; D009638:Norepinephrine