Experimental neurology · 2016
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.
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Reick Christiane, Ellrichmann Gisa, Tsai Teresa, Lee De-Hyung, Wiese Stefan, Gold Ralf, Saft Carsten, Linker Ralf A
Аннотация
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.
Предметные рубрики MeSH
AnimalsAnimals, NewbornAstrocytesBrain-Derived Neurotrophic FactorCaspase 3Cells, CulturedCulture Media, ConditionedDisease Models, AnimalDose-Response Relationship, DrugExploratory BehaviorGene Expression RegulationGlatiramer AcetateGlial Fibrillary Acidic ProteinHumansHuntingtin ProteinHuntington DiseaseImmunosuppressive AgentsMesencephalonMiceMice, Inbred C57BLMice, TransgenicMutationNerve DegenerationRNA, Messenger