Interaction between nerve growth factor and GM1 monosialoganglioside in preventing cortical choline acetyltransferase and high affinity choline uptake decrease after lesion of the nucleus basalis.
Monosialoganglioside GM1 and nerve growth factor (NGF) were administered alone or concomitantly to adult male rats with a unilateral ibotenic acid lesion of the nucleus basalis magnocellularis (NBM). High-affinity choline uptake (HACU) rate and choline acetyltransferase (ChAT) activity were measured, 4 and 21 days after surgery, respectively, in the frontal and parietal cortices of both hemispheres. A 33-34% decrease in HACU rate and a 43-39% decrease in ChAT activity was found in the ipsilateral cortices 4 and 21 days, respectively, after the lesion. If the lesioned rats received NGF (10 micrograms i.c.v.) twice a week or daily administrations of GM1 (30 mg/kg, i.p.), beginning immediately after surgery the decrease in HACU rate and ChAT activity was smaller. If NGF and GM1 were given concomitantly no decrease in HACU rate and ChAT activity was detected in the lesioned hemisphere and a slight increase occurred in the contralateral hemisphere. However, after the concurrent administration of NGF (10 micrograms i.c.v.) and the inactive dose of GM1 10 mg/kg i.p. no decrease in HACU and ChAT activity was also found in the lesioned rats. The latter finding indicates a potentiation by GM1 of NGF effects on the cholinergic neurons of the NBM. The two drugs may either antagonize the neurotoxic effects of ibotenic acid or stimulate a compensatory activity in the remaining neurons.
Di Patre
P L
PL
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Casamenti
F
F
Cenni
A
A
Pepeu
G
G
D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism*; D002794:Choline / Q000493:pharmacokinetics*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004347:Drug Interactions; D005732:Gangliosides / Q000494:pharmacology*; D007051:Ibotenic Acid; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005732:Gangliosides; D009414:Nerve Growth Factors; C025447:sialogangliosides; D007051:Ibotenic Acid; D002795:Choline O-Acetyltransferase; D002794:Choline