Neurotrophic effects of G(M1) ganglioside, NGF, and FGF2 on canine dorsal root ganglia neurons in vitro

Dogs share many chronic morbidities with humans and thus represent a powerful model for translational research. In comparison to rodents, the canine ganglioside metabolism more closely resembles the human one. Gangliosides are components of the cell plasma membrane playing a role in neuronal development, intercellular communication and cellular differentiation. The present in vitro study aimed to characterize structural and functional changes induced by G(M1) ganglioside (G(M1)) in canine dorsal root ganglia (DRG) neurons and interactions of G(M1) with nerve growth factor (NGF) and fibroblast growth factor (FGF2) using immunofluorescence for several cellular proteins including neurofilaments, synaptophysin, and cleaved caspase 3, transmission electron microscopy, and electrophysiology. G(M1) supplementation resulted in increased neurite outgrowth and neuronal survival. This was also observed in DRG neurons challenged with hypoxia mimicking neurodegenerative conditions due to disruptions of energy homeostasis. Immunofluorescence indicated an impact of G(M1) on neurofilament phosphorylation, axonal transport, and synaptogenesis. An increased number of multivesicular bodies in G(M1) treated neurons suggested metabolic changes. Electrophysiological changes induced by G(M1) indicated an increased neuronal excitability. Summarized, G(M1) has neurotrophic and neuroprotective effects on canine DRG neurons and induces functional changes. However, further studies are needed to clarify the therapeutic value of gangliosides in neurodegenerative diseases.