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Astrocyte-Secreted Factors Selectively Alter Neural Stem and Progenitor Cell Proliferation in the Fragile X Mouse
Mary Sourial1, Laurie C Doering1
1McMaster Integrative Neuroscience Discovery and Study, McMaster University, HamiltonON, Canada; Pathology and Molecular Medicine, McMaster University, HamiltonON, Canada.
Frontiers in Cellular Neuroscience
|June 1, 2016
Summary
Astrocyte-secreted factors influence neural stem and progenitor cell proliferation in Fragile X syndrome. Fragile X astrocyte factors alter neural stem cell responses, impacting brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Astrocytes play a crucial role in regulating neural stem and progenitor cell production during brain development.
- The impact of astrocyte function on cell production in neurodevelopmental disorders, such as Fragile X syndrome, remains largely unknown.
Purpose of the Study:
- To investigate the effect of astrocyte-conditioned media (ACM) on neural stem and progenitor cell proliferation in the Fragile X mouse model.
- To identify differentially expressed astrocyte-secreted proteins in Fragile X mouse brains.
Main Methods:
- Neural Colony Forming Cell assay was used to assess neurosphere generation from progenitor cells and stem cells exposed to ACM.
- Two-dimensional Differential Gel Electrophoresis (2D DIGE) was employed to identify astrocyte-secreted proteins with differential expression between wild-type (WT) and Fmr1-knockout (KO) mice.
Main Results:
- ACM from both WT and Fmr1-KO mice resulted in a higher percentage of smaller neurospheres, indicating restricted progenitor cell proliferation in Fmr1-KO brains.
- WT neurospheres, but not KO neurospheres, showed enhanced responses to Fmr1-KO ACM, with an increased percentage of large neurospheres (neural stem cells).
- Differential expression of astrocyte-secreted proteins between Fmr1-KO and WT cortices and hippocampi was identified.
Conclusions:
- Astrocytes critically govern neural cell production during brain development.
- Fragile X syndrome exhibits significant alterations in neural cell proliferation due to astrocyte-secreted factors.
- Astrocyte-secreted factors with differential expression in Fragile X brains were identified, highlighting their role in neural precursor cell biology.
