Exogenous gangliosides increase the release of brain-derived neurotrophic factor

Gangliosides are lipophilic compounds found in cell plasma membranes throughout the brain that play a role in neuronal plasticity and regeneration. Indeed, absence or abnormal accumulation of gangliosides has been shown to lead to neurological disorders. Experimental data have shown that exogenous gangliosides exhibit properties similar to the neurotrophins, a family of neurotrophic factors that are important in the survival and maintenance of neurons and prevention of neurological diseases. Brain-derived neurotrophic factor (BDNF) is the most abundant of the neurotrophins. This work was done to reveal the neurotrophic mechanism of exogenous gangliosides. In particular, we examined whether gangliosides promote the release of BDNF. Rat hippocampal neurons or human neuroblastoma cells were transduced with a recombinant adenovirus expressing BDNF-flag to facilitate detection of BDNF. Release of BDNF was then determined by Western blot analysis and a two-site immunoassay of culture medium. The depolarizing agent KCl was used as a comparison. In hippocampal neurons, both GM1 ganglioside and KCl evoked within minutes the release of mature BDNF. In human cells, GM1 and other gangliosides released both mature BDNF and pro-BDNF. The effect of gangliosides was structure-dependent. In fact, GT1b preferentially released mature BDNF whereas GM1 released both mature and pro-BDNF. Ceramide and sphingosine did not modify the release of BDNF. This work provides additional experimental evidence that exogenous gangliosides can be used to enhance the neurotrophic factor environment and promote neuronal survival in neurological diseases. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.