γ-Synuclein Induces Human Cortical Astrocyte Proliferation and Subsequent BDNF Expression and Release.
Neuroscience
; 410: 41-54, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-31078687
ABSTRACT
γ-Synuclein (γ-syn) is expressed by astrocytes in the human nervous system, and increased extracellularly in the brain and cerebrospinal fluid of individuals diagnosed with Alzheimer's disease. Upregulation of γ-syn also coincides with proliferation of glioblastomas and other cancers. In order to better understand regulation and function of extracellular γ-syn, primary human cortical astrocytes were treated with γ-syn conditioned media at various physiological concentrations (50, 100, 150â¯nM) after cell synchronization. Additionally, extracellular brain-derived neurotrophic factor (BDNF), a neuroprotective growth factor released by astrocytes that has been shown to be decreased extracellularly in neurodegenerative disease, was observed in response to γ-syn treatment. Analysis of 5-bromodeoxyuridine (BrdU) and propidium iodide through flow cytometry 24â¯h after release from synchronization revealed an increase in G2/M phase of the cell cycle with 100â¯nM γ-syn during initial cell division, an effect that was reversed at 48â¯h. However, increased extracellular BDNF was observed at 48â¯h with 100â¯nM and 150â¯nM γ-syn treatment with no difference between controls at 24â¯h. Further analysis of cell cycle markers with immunocytochemistry of BrdU and Ki67 after treatment with 100â¯nM γ-syn confirmed increased initial cell proliferation and decreased non-proliferating cells. Western blot analysis demonstrated increased γ-syn levels after 100â¯nM treatment at 24 and 48â¯h, and increased pro-BDNF, mature BDNF and cell viability at 48â¯h. The results demonstrate that γ-syn internalization by human cortical astrocytes causes upregulation of the cell cycle, followed by subsequent BDNF expression and release.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Córtex Cerebral
/
Astrócitos
/
Fator Neurotrófico Derivado do Encéfalo
/
Proliferação de Células
/
Gama-Sinucleína
Limite:
Humans
Idioma:
En
Revista:
Neuroscience
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos