GM1-pentasaccharide (osGM1) prevents damage on dopaminergic system in a mouse model of Parkinson´s disease

BISIG CG; DITAMO Y; RODRIGUEZ-WALKER, M; FARIAS, G; RODRIGUEZ, PEA

Carlos Paz

Congreso; XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2019

Sociedad Argentina de Investigación en Neurociencias

Glycosphingolipids (GSLs) are components of most cell membranes and are particularly abundant in the nervous system. GSLs play important roles in neuronal development and survival and modulate a variety of cell activities. Several mechanisms have been proposed to explain the biological effect of GSLs, although a complete understanding of them is still missing. Exogenously administered GSLs (gangliosides in particular) have been clinically tested for treatment of several diseases and it has been demonstrated that short-term use of monosialoganglioside GM1 resulted in significant symptoms reduction in Parkinson?s disease (PD) patients. In vitro and in vivo experiments showed that GM1 exerts neurotrophic functions by interacting with plasma membrane proteins through its oligosaccharide portion (osGM1). We investigate the response of the damaged dopamine system to osGM1 in the neurotoxin 1-methyl-4-phenyl-1,2,3,6-terahydropyridine (MPTP)-induced model of PD in mice. 30.0 mg/kg of osGM1 administered to young C57/BL6J mice with severe striatal dopamine depletion (approx 90%) caused an increase in striatal dopamine levels. This effect was not apparent at a higher dose (60 mg/kg). These results show that osGM1 can partially restore striatal dopamine levels in MPTP-treated mice. osGM1 may lead to the development of new types of useful neuroactive compounds for Parkinson´s disease treatment.