title: 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.
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.
authors: 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.
authors: Christiane
authors: C
authors: Reick
authors: Department of Neurology St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany. Electronic address: gisa.ellrichmann@rub.de.
authors: Gisa
authors: G
authors: Ellrichmann
authors: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany.
authors: Teresa
authors: T
authors: Tsai
authors: Department of Neurology, Friedrich-Alexander-University Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors: De-Hyung
authors: DH
authors: Lee
authors: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany.
authors: Stefan
authors: S
authors: Wiese
authors: 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.
authors: Ralf
authors: R
authors: Gold
authors: Department of Neurology St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany.
authors: Carsten
authors: C
authors: Saft
authors: Department of Neurology, Friedrich-Alexander-University Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors: Ralf A
authors: RA
authors: Linker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D000068717:Glatiramer Acetate / Q000494:pharmacology / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics; D006816:Huntington Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; C086055:HTT protein, human; D000071058:Huntingtin Protein; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D000068717:Glatiramer Acetate; D053148:Caspase 3
keywords: Astrocytes; BDNF; Glatiramer acetate; Huntington's disease; Neuroprotection