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

Christiane Reick; Gisa Ellrichmann; Teresa Tsai; De-Hyung Lee; Stefan Wiese; Ralf Gold; Carsten Saft; Ralf A Linker

doi:10.1016/j.expneurol.2016.08.012

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

Exp Neurol. 2016 Nov;285(Pt A):12-23. doi: 10.1016/j.expneurol.2016.08.012. Epub 2016 Aug 29.

Authors

Christiane Reick¹, Gisa Ellrichmann², Teresa Tsai³, De-Hyung Lee⁴, Stefan Wiese³, Ralf Gold¹, Carsten Saft⁵, Ralf A Linker⁴

Affiliations

¹ Department of Neurology St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany; International Graduate School of Neuroscience, Ruhr-University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany.
² Department of Neurology St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany. Electronic address: [email protected].
³ Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany.
⁴ Department of Neurology, Friedrich-Alexander-University Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
⁵ Department of Neurology St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany.

PMID: 27587303
DOI: 10.1016/j.expneurol.2016.08.012

Abstract

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.

Keywords: Astrocytes; BDNF; Glatiramer acetate; Huntington's disease; Neuroprotection.

MeSH terms

Animals
Animals, Newborn
Astrocytes / chemistry
Astrocytes / drug effects*
Brain-Derived Neurotrophic Factor / genetics
Brain-Derived Neurotrophic Factor / metabolism*
Caspase 3 / metabolism
Cells, Cultured
Culture Media, Conditioned / pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Exploratory Behavior / drug effects
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics
Glatiramer Acetate / pharmacology
Glatiramer Acetate / therapeutic use*
Glial Fibrillary Acidic Protein / metabolism
Humans
Huntingtin Protein / genetics
Huntington Disease / complications
Huntington Disease / drug therapy*
Huntington Disease / genetics
Huntington Disease / pathology*
Immunosuppressive Agents / pharmacology
Immunosuppressive Agents / therapeutic use*
Mesencephalon / cytology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation / genetics
Nerve Degeneration / drug therapy
Nerve Degeneration / etiology
RNA, Messenger / metabolism

Substances

Brain-Derived Neurotrophic Factor
Culture Media, Conditioned
Glial Fibrillary Acidic Protein
HTT protein, human
Huntingtin Protein
Immunosuppressive Agents
RNA, Messenger
Glatiramer Acetate
Caspase 3