Limited neocortical devascularizing lesions causing deficits in memory retention and choline acetyltransferase activity--effects of the monosialoganglioside GM1.
In mature rats with unilateral cortical lesions, choline acetyltransferase activity was found to decrease by 40% in the ipsilateral nucleus basalis magnocellularis, compared with control animals. Intraventricular administration of the monosialoganglioside GM1 (5 mg/kg per day), via minipumps, over a period of 14 days prevented this fall in choline acetyltransferase activity. The activity of this enzyme in the sham operated subjects was not significantly different from that in the unoperated group. This biochemical data is in full agreement with regards to the protective action of monosialoganglioside GM1 on forebrain cholinergic neurons. In this study the behavioral effects of these cortical lesions were investigated for the first time. Results show that these lesions, with their associated retrograde neuronal degenerative effects, altered a variety of sensorimotor and memory-based behaviors. In particular, the limited unilateral devascularization of the neocortex increased baseline locomotor activity above control; affected motor coordination; impaired passive avoidance retention and reacquisition; and decreased the retention of learnt Morris water-maze information. Infusion of the monosialoganglioside into the ventricles, whilst having no effect on the increased motor activity or motor coordination deficit, did enhance the reacquisition of information in both memory-related tasks.
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
P J
PJ
Elliott
L
L
Garofalo
A C
AC
Cuello
D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000494:pharmacology* / Q000627:therapeutic use; D007276:Injections, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D009069:Movement Disorders / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D005677:G(M1) Ganglioside; D002795:Choline O-Acetyltransferase