Lesions of the nucleus basalis magnocellularis in the rat: morphological, biochemical and behavioral reparative effect of nerve growth factor and ganglioside GM1.
Three- and fifteen-month old rats with a unilateral ibotenic acid lesion of the nucleus basalis magnocellularis (NBM) were used. In 3-month old rats, 4 days after the lesion a 34 and 33% decrease in high affinity choline uptake (HACU) rate was found in the ipsilateral frontal and parietal cortices, respectively. Twenty-one days later the lesioned rats showed a loss in the NBM choline acetyltransferase (ChAT)-positive cells, a marked decrease in ipsilateral cortical ChAT activity and an impairment of the acquisition of a passive avoidance conditioned response. If the lesioned rats received nerve growth factor (NGF) (10 micrograms i.c.v.) twice a week or daily administration of ganglioside GM1 (GM1) (30 mg/kg i.p.), beginning immediately after surgery, the decreases in the HACU rate and ChAT activity were significantly smaller and the behavioral performance was normal. A potentiation by GM1 of NGF effects on the cholinergic neurons of the NBM occurred since no differences were detected between sham-operated rats and rats trated with NGF plus either the active (30 mg/kg) or inactive (10 mg/kg) dose of GM1. The loss in the number of NBM ChAT-positive neurons was reduced by GM1 or prevented by NGF administrations, indicating that the two drugs prevent the cholinergic deficit by protecting the cholinergic neurons of the NBM from ibotenic acid neurotoxicity. GM1 had no effect on ChAT activity decrease and behavioral impairment in 15-month old rats. The latter finding indicates an age-related loss of the ability of GM1 to enhance neurotrophic activity in the NBM.
Casamenti
F
F
Department of Preclinic and Clinic Pharmacology, University of Florence, Italy.
Milan
F
F
Pepeu
G
G
D000818:Animals; D001930:Brain Injuries / Q000201:enzymology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013377:Substantia Innominata / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
D009414:Nerve Growth Factors; D005677:G(M1) Ganglioside; D002795:Choline O-Acetyltransferase; D002794:Choline