Effect of nerve growth factor and GM1 ganglioside on the recovery of cholinergic neurons after a lesion of the nucleus basalis in aging rats.
A unilateral ibotenic acid lesion was placed in the nucleus basalis magnocellularis of 3- and 18-month-old rats. In the lesioned aging rats, the number of choline acetyltransferase-immunoreactive neurons of the nucleus basalis magnocellularis was markedly reduced in the ipsilateral side and to a lesser extent in the contralateral side. Twenty-one days after the lesion, the activity of choline acetyltransferase in the ipsilateral cortex was reduced by 40% in both groups of rats and by 24% in the contralateral frontal cortex of the aging rats. Intracerebroventricular administration of nerve growth factor (10 micrograms twice a week) to aging lesioned rats for 3 weeks after surgery resulted in a complete recovery in the number of choline acetyltransferase-immunoreactive neurons in the nucleus basalis of both sides, and choline acetyltransferase activity in the contralateral cortex, with little effect on the ipsilateral cortex. No potentiation was seen after the concurrent administration of GM1 ganglioside and nerve growth factor. Complete recovery in cortical choline acetyltransferase activity was only observed in the lesioned rats treated with nerve growth factor for 1 week before and 3 weeks after lesioning. Nerve growth factor treatment, both after the lesion, and before and after the lesion, improved the passive avoidance performance disrupted by the lesion. In young lesioned rats daily intraperitoneal administration of GM1 (30 mg/kg) for 21 days after surgery promoted both the recovery of choline acetyltransferase activity and passive avoidance performance. In aging rats GM1, even at a dose twice as large, failed to reverse the biochemical and morphological deficits and behavioral impairment induced by the lesion. Only when GM1 administration was started 3 days before the lesion, were a complete recovery in choline acetyltransferase activity in the contralateral cortex and a partial recovery in the ipsilateral cortex obtained. Our results indicate that nerve growth factor and, to some extent, GM1 facilitate the recovery of the cholinergic neurons after a lesion of the nucleus basalis in aging rats, but their efficacy is reduced. The lower efficacy of GM1 as compared to NGF might be due to the different routes of administration used.
Casamenti
F
F
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Scali
C
C
Giovannelli
L
L
Faussone-Pellegrini
M S
MS
Pepeu
G
G
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000187:drug effects; D002799:Cholinergic Fibers / Q000502:physiology*; D005732:Gangliosides / Q000494:pharmacology*; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016548:Prosencephalon / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013377:Substantia Innominata / Q000276:immunology / Q000648:ultrastructure*
D005732:Gangliosides; D009414:Nerve Growth Factors; D007051:Ibotenic Acid; D002795:Choline O-Acetyltransferase