The effect of the ganglioside GM 1 on neuronal plasticity

Not only developing but also adult mammalian central nervous system (CNS) seems to possess an intrinsic capacity for functional repair after damage. The irreversibly damaged neurons are partly substituted by alternative pathways in the course of massive sprouting and reactive synaptogenesis with intact undamaged axons... 3 5.x Rate and degree of this synaptic remodelling varies with age, localization and type of neuronal injury. The molecular mechanisms determining this remodelling are still unknown but presumably involve appropriate signals from adjacent environment, denervated target areas and brain regions distant from the damaged area. Support to this latter conclusion comes from experiments where the effect of the ganglioside GM1 (for nomenclature see Svennerholm”) as a pharmacological agent favoring the recovery of synaptic function and as a tool for understanding the compensatory mechanisms triggered by brain injury is investigated. After a partial mechanical lesion of the dopaminergic nigro-striatal system, chronic administration of the ganglioside GM1 facilitates the recovery of dopamine synaptic function, as indicated by the decreased sensitivity to apomorphine-induced rotational behavior.’ There is a concomitant stimulation of the collateral sprouting of the intact dopaminergic nerve terminals in the striatum and a larger survival of dopaminergic zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA cells in the substantia nigra of the hemitransected side.“.‘” More recently we have found that GM1 exerts its functional reparative effect only under certain conditions (Fig. 1). For instance, an almost complete lesion of the ascending dopaminergic fibers renders GM, inactive,*’ presumably as a reflection of the extent of the lesion. The effect of GM, on striatal tyrosine hydroxylase (TH) of partially unilaterally hemitransected rats is also abolished