Expression of brain-derived neurotrophic factor in astrocytes - Beneficial effects of glatiramer acetate in the R6/2 and YAC128 mouse models of Huntington's disease

• Glatiramer acetate improves clinical course of R6/2 and YAC128 mice.
• Glatiramer acetate significantly prolongs survival in R6/2 mice.
• Glatiramer acetate leads to neuroprotection in Huntington's disease mice.
• Astrocytes are involved in the neuroprotective effect via BDNF production.

Glatiramer acetate (GA) is a FDA-approved drug which is licensed for the treatment of relapsing-remitting multiple sclerosis and which may exert neuroprotective effects via brain-derived neurotrophic factor (BDNF).In this study, we investigate effects of GA on BDNF expression especially in astrocytes in vitro and in vivo in brains of R6/2 and YAC128 transgenic mouse models of Huntington's disease (HD) where a pathogenic role of astroglial cells has recently been shown. We show that GA increases the expression of functionally active BDNF in astrocyte culture and in astrocytes of GA treated HD mice. In the brains of these mice, GA decreases neurodegeneration and restores BDNF levels. The beneficial effect of GA in R6/2 mice also comprises reduced weight loss and prolonged life span and, for both models, also improved motor performance. Further studies with this safe and effective drug in HD are warranted.