Specific Alterations in Astrocyte Properties via the GluA2-GAPDH Complex Associated with Multiple Sclerosis
Autor: | Clement C. Zai, Fang Liu, Anlong Jiang, Frankie H. F. Lee, Hailong Zhang |
---|---|
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Encephalomyelitis Autoimmune Experimental Multiple Sclerosis lcsh:Medicine Fluorescent Antibody Technique Permeability Article Mice 03 medical and health sciences 0302 clinical medicine Mediator In vivo medicine Animals Receptors AMPA lcsh:Science Receptor Neuroinflammation Glyceraldehyde 3-phosphate dehydrogenase Aquaporin 4 Multidisciplinary biology Chemistry Multiple sclerosis lcsh:R medicine.disease Mitochondria Cell biology Astrogliosis Excitatory Amino Acid Transporter 1 Disease Models Animal 030104 developmental biology medicine.anatomical_structure Excitatory Amino Acid Transporter 2 Blood-Brain Barrier Astrocytes biology.protein lcsh:Q Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) Biomarkers 030217 neurology & neurosurgery Protein Binding Astrocyte |
Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-17 (2018) |
ISSN: | 2045-2322 |
Popis: | There is strong evidence indicating neuroinflammation is an important mediator in multiple sclerosis (MS), with astrogliosis playing a significant role in this process. Surprisingly, astrocytes exert paradoxical roles during disease development, but the mechanisms remain unknown. Previously, we have reported that administering an interfering peptide (GluA2-G-Gpep) which specifically disrupts the GluA2-GAPDH interaction rescued neurological symptoms in the EAE mouse model of MS. In this study, we validated that the GluA2-GAPDH complex was elevated in LPS-induced primary reactive astrocytes, and GluA2-G-Gpep treatment significantly reduced GFAP expression levels in both EAE mice and reactive astrocytes. Further in vivo and in vitro analyses revealed that GluA2-G-Gpep administration normalized EAAT1 and EAAT2 expression, rescued compromised blood-brain barrier integrity via AQP4, promoted actin reorganization and changed mitochondrial dynamics. These alterations may partially be explained by changes in the nuclear GAPDH and p53 transcription pathways. Our findings provide critical implications for understanding the astrocyte properties regulated by GluA2-GAPDH associated with MS, and insights for novel treatment options targeting at astrocytes. |
Databáze: | OpenAIRE |
Externí odkaz: |