NERVE GROWTH-FACTOR AND THE MONOSIALOGANGLIOSIDE GM1 - ANALOGOUS AND DIFFERENT IN-VIVO EFFECTS ON BIOCHEMICAL, MORPHOLOGICAL, AND BEHAVIORAL PARAMETERS OF ADULT CORTICALLY LESIONED RATS

This study examined the behavioral effects of maximal doses of exogeno us NGF and/or GM1 when given intracerebroventricularly to adult rats w ith unilateral cortical lesions. In addition, the long-term effects of these agents on choline acetyltransferase (ChAT), glutamic acid decar boxylase (GAD) activity, and choline uptake, as well as on ChAT and NG F receptor (p75(NGFR)) immunoreactivity in various brain regions, were also investigated. When retested in passive avoidance and Morris wate r maze tasks, 30 days postlesion (i.e., 2 weeks after termination of t reatment), decorticated vehicle-treated rats showed retention and reac quisition deficits which were equally attenuated by NGF (6 mu g/day, 1 4 days) or NGF + GM1 (750 mu g/day, 14 days) treatment. By contrast, l esioned animals which received GM1 alone only showed improved reacquis ition of the two tasks. After behavioral testing (52 days postlesion) lesioned vehicle-treated animals had decreased ChAT activity in the ip silateral nucleus basalis magnocellularis (NBM) but not in other subco rtical brain areas examined. Neuronal loss was observed only in the ve ntrolateral nucleus of the ipsilateral dorsal thalamus. However, using quantitative image analysis a significant shrinkage of ChAT immunorea ctive (IR) and p75(NGFR)-IR NBM neurons as well as a decrease in their neuritic network was noted, particularly in the mid portion of the NB M. GM1 and NGF equally prevented these deficits in the NBM and, furthe rmore, enhanced ChAT activity and choline uptake in the remaining cort ex ipsilateral to the lesion site. These alterations in NBM and cortic al cholinergic markers were even more augmented in rats which received both NGF and GM1 treatment. By contrast, the noted NGF-induced increa se in striatal ChAT activity was not further increased by concomitant GM1 treatment. GAD activity in all brain areas examined was unaltered by the lesion or any of the treatments and the apparent thalamic neuro nal retrograde degeneration was not prevented by any of the treatments , It is concluded that GM1 or NGF treatment can distinctly affect perf ormance of cortically lesioned rats in passive avoidance and Morris wa ter maze tasks despite their equal ability to serve as long-term neuro protective agents for the basalo-cortical cholinergic pathway. (C) 199 4 Academic Press, Inc.