INDUCTION OF MEMORY AND CORTICAL CHOLINERGIC NEUROCHEMICAL RECOVERY WITH COMBINE FETAL TRANSPLANTATION AND GM1 TREATMENTS IN RATS WITH LESIONS OF THE NBM

Sixty-four Sprague-Dawley rats received ibotenic-acid-induced unilater al nucleus basalis of Meynert (nbM) lesions; 10 additional animals ser ved as sham controls. Eight to ten days later, subjects with lesions r eceived either fetal cholinergic transplants implanted within the ipsi lateral (relative to the lesion) frontal cortex or control transplant surgeries. Lesioned animals with and without transplants were then tre ated with GM1 (20 mg/kg, i.p.) for either 0, 1 or 10 days and were the n trained and tested for 72-hour retention of passive avoidance. Resul ts indicated that the lesion produced a significant impairment on this task. Transplant therapy combined with GM1 for 10 days yielded a sign ificant reversal of this deficit. GM1 injections continued once per we ek for 4 weeks for half the lesioned animals in the transplant and no- transplant 10-day conditions. During a 6-month period, all subjects we re assessed on two additional memory tasks (complex spatial discrimina tion and delayed spatial alternation). In general, there was no indica tion of a lesion, transplant, GM1, or transplant X GM1 effect on these tasks. Approximately 7.5 months after transplants, subjects were sacr ificed and their frontal cortices examined for choline acetyltransfera se (CAT) and acetylcholinesterase ( AChE) activity. Only lesioned subj ects with transplants which were given sustained GM1 treatment (i.e., 10 days plus weekly injections for 4 weeks) showed significant attenua tions of lesion-induced CAT and AChE depletions. These data suggest th at a combined treatment strategy of fetal transplant plus GM1 is capab le of reversing nbM lesion-induced memory and neurochemical deficits i n an animal model of the cholinergic deficits in Alzheimer's disease.