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Published on: November 8, 2016
Selective cell-cycle arrest and induction of apoptosis in proliferating neural cells by ganglioside GM3
1Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Abstract:
Control of cell proliferation and cell survival is critical during development of the vertebrate central nervous system (CNS). Much of the cell death seen during early stages of CNS development occurs through apoptosis; however, the factors that induce this early apoptosis are not clearly understood. Gangliosides, sialylated glycosphingolipids, are expressed in the CNS and have been proposed to regulate cell growth and differentiation. Here we show that the simple ganglioside GM3 selectively inhibits the proliferation of and induces apoptosis of actively dividing astrocyte precursors and other neural progenitors. The inhibition of astrocyte precursor proliferation by GM3 appears to be mediated in part by the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1). During neonatal development there is extensive cell proliferation and little apoptosis in the ventricular and subventricular zones of the CNS. This proliferation was dramatically inhibited and the degree of apoptosis dramatically increased following intraventricular administration of GM3. These data suggest that GM3, a simple ganglioside, may regulate cell proliferation and death in the CNS and as such may have potential for brain tumor therapy.
Insights
The simple ganglioside GM3 inhibits neural progenitor proliferation and induces apoptosis in the developing central nervous system (CNS). This finding suggests GM3
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Cell proliferation and survival are crucial for vertebrate central nervous system (CNS) development.
- Early CNS development involves significant apoptosis, but its inducers are not fully understood.
- Gangliosides, including GM3, are sialylated glycosphingolipids found in the CNS, potentially regulating cell growth.
Purpose of the Study:
- To investigate the role of the simple ganglioside GM3 in regulating cell proliferation and apoptosis in the developing CNS.
- To determine if GM3 affects neural progenitor cells, such as astrocyte precursors.
Main Methods:
- Administered GM3 intraventricularly to neonatal rodents.
- Assessed the effects of GM3 on cell proliferation and apoptosis in the CNS ventricular and subventricular zones.
- Investigated the involvement of the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) in GM3-mediated inhibition of astrocyte precursor proliferation.
Main Results:
- GM3 selectively inhibited proliferation and induced apoptosis in actively dividing astrocyte precursors and other neural progenitors.
- Intraventricular GM3 administration significantly reduced proliferation and increased apoptosis in the neonatal CNS ventricular and subventricular zones.
- GM3-induced inhibition of astrocyte precursor proliferation was partly mediated by the Cdk inhibitor p27(Kip1).
Conclusions:
- The simple ganglioside GM3 plays a regulatory role in controlling cell proliferation and death within the developing CNS.
- GM3's ability to inhibit neural progenitor proliferation and induce apoptosis suggests potential therapeutic applications for brain tumors.
