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: Christiane Reick, Gisa Ellrichmann, Teresa Tsai, De-Hyung Lee, Stefan Wiese, Ralf Gold, Carsten Saft, Ralf A Linker
• Journal: Experimental neurology (Exp Neurol) Vol. 285 Issue Pt A Pg. 12-23 (Nov 2016) ISSN: 1090-2430 [Electronic] United States
• PMID: 27587303 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Animals
• Animals, Newborn
• Astrocytes (chemistry, drug effects)
• Brain-Derived Neurotrophic Factor (genetics, 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, genetics)
• Glatiramer Acetate (pharmacology, therapeutic use)
• Glial Fibrillary Acidic Protein (metabolism)
• Humans
• Huntingtin Protein (genetics)
• Huntington Disease (complications, drug therapy, genetics, pathology)
• Immunosuppressive Agents (pharmacology, therapeutic use)
• Mesencephalon (cytology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutation (genetics)
• Nerve Degeneration (drug therapy, etiology)
• RNA, Messenger (metabolism)