Background Brain-derived neurotrophic factor (BDNF) is most likely involved in the pathogenesis of HD. Impaired transcription and transport of BDNF finally result in decreased brain levels of BDNF in HD. GA exerts neuroprotective effects via increased BDNF upregulation in astrocytes and neurons rather than in immune cells of the periphery.
Aims To investigate neuroprotective effects and therapeutic efficacy of glatiramer acetate (GA) in a transgenic animal model of Huntington's disease.
Methods/techniques R6/2 transgenic mice were immunised subcutaneously with GA or with ovalbumin as control and the clinical course was monitored daily. Coronal brain sections were immune- and histochemically processed for Cresyl violet-, Ubiquitin-, NeuN-, GFAP- and BDNF-staining. Quantitative real time PCR was performed to investigate potential differences in BDNF expression in the brain within the different groups. To analyse the effect of GA on astrocytes, in vitro stimulation of primary astrocyte cultures with GA and astrocytes viability assay were performed.
Results Neurodegeneration and astrogliosis were reduced after GA treatment. Furthermore, first results indicate a possible bystander effect of astrocytes in GA mediated neuroprotection in R6/2 mice. Analysis of immunofluorescence shows a raised number of BDNF positive astrocytes. Improvement in motor function and dyskinesia after GA treatment were underlined by both real time PCR, showing restored BDNF levels and immunofluorescence.
Conclusion Our results provide evidence for neuroprotection in an animal model of Huntington's disease mediated by GA. This neuroprotection may be linked to an upregulation of BDNF in Huntington's Disease. Based on our findings, we propose a direct action of GA on astrocytes with beneficial effects on neurons.
- glatiramer acetate
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