Effects of Chronic GM1 Ganglioside Treatment on Nigral Dopamine Cell Bodies and Dendrites in Experimental Rats Using Image Analysis — Relationship to the Pharmacokinetic Properties

Abstract

Previous studies have shown that chronic treatment with the GM1 ganglioside can increase the survival of dopamine nerve cell bodies in the substantia nigra, mainly in the caudal part on the lesioned side, following a partial unilateral hemitransection (Agnati et al. 1983, 1984; Toffano et al. 1983). It was also demonstrated that chronic treatment with the ganglioside GM1 increase tyrosine hydroxylase immunoreactivity within the rostral- ly located dopamine nerve cells present close to the site of the lesion (Agnati et al. 1984). Also it was found that chronic GM1 ganglioside treatment increases the density of tyrosine hydroxylase immunoreactive dendrites in the zona reticulata of the lesioned side as shown at several rostrocaudal levels. These results were interpreted to indicate that chronic GM1 treatment can exert an excitatory metabolic action on dopamine nerve cells present close to the lesion which may lead to enhanced production of neuronal trophic factors diffusing out in the substantia nigra and causing an increased survival of the less severely lesioned dopamine nerve cells present within the caudal part of the substantia nigra (see Agnati et al. 1984). In the present paper we have continued these studies by using the IBAS Image Analyzer (Zeiss-Kontron) to evaluate the action of chronic GM1 treatment on the dopamine cell bodies and dendrites in the substantia nigra of the lesioned and unlesioned side. In order to further understand the mechanism of action underlying the neurotrophic activity of GM1 treatment, the pharmacokinetic characteristics of GM1 has been studied and compared in control rats and in rats with a unilateral partial hemitransection.