γ-Synuclein Induces Human Cortical Astrocyte Proliferation and Subsequent BDNF Expression and Release

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• γ-Synuclein (γ-syn) is implicated in Alzheimer's disease and cancer.
• Extracellular γ-syn and its role in astrocyte function require further investigation.
• Brain-derived neurotrophic factor (BDNF) is crucial for neuronal health but decreases in neurodegenerative conditions.

Purpose of the Study:

• To investigate the effects of extracellular γ-syn on primary human cortical astrocytes.
• To examine the impact of γ-syn on astrocyte cell cycle regulation.
• To determine the influence of γ-syn on BDNF expression and release.

Main Methods:

• Primary human cortical astrocytes were treated with varying concentrations of γ-syn conditioned media.
• Cell synchronization and cell cycle analysis were performed using flow cytometry (BrdU, propidium iodide).
• Immunocytochemistry (BrdU, Ki67) and Western blot were used to assess cell proliferation, cell cycle markers, γ-syn, and BDNF levels.

Main Results:

• γ-Syn treatment (100nM) initially increased astrocyte cell cycle progression (G2/M phase) at 24h, which was reversed at 48h.
• Extracellular BDNF levels increased at 48h following treatment with 100nM and 150nM γ-syn.
• γ-Syn treatment enhanced astrocyte proliferation, increased γ-syn levels, and upregulated pro-BDNF, mature BDNF, and cell viability at 48h.

Conclusions:

• γ-Syn internalization by astrocytes stimulates cell cycle progression.
• Astrocyte exposure to γ-syn leads to subsequent upregulation and release of BDNF.
• These findings suggest a novel role for γ-syn in astrocyte-mediated neuroprotection and potentially in disease pathogenesis.