Neuronal apoptosis in mouse trisomy 16: mediation by caspases
1Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA.
Journal of Neurochemistry
|March 31, 1999
Summary
Trisomy 16 (Ts16) mouse neurons undergo accelerated apoptosis, a cell death pathway involving caspases. This finding provides insights into neurodegenerative disorders like Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Trisomy 16 (Ts16) mice serve as a model for Down syndrome (trisomy 21).
- Ts16 mouse hippocampal neurons exhibit accelerated cell death in vitro.
- Alzheimer's disease (AD) involves neuronal death, potentially through apoptosis.
Purpose of the Study:
- To investigate the mechanism of accelerated neuronal death in Ts16 mouse hippocampal neurons.
- To determine if apoptosis is involved in Ts16 neuronal cell death.
- To explore the role of caspases in Ts16 neuronal apoptosis.
Main Methods:
- Terminal transferase-mediated dUTP nick end-labeling (TUNEL) assay to detect DNA fragmentation.
- Treatment with caspase inhibitors to assess their effect on neuronal survival.
- Comparison of Ts16 neuron survival with control neurons in the presence of caspase inhibitors.
Main Results:
- Dying Ts16 neurons displayed pyknotic nuclei and DNA fragmentation, indicative of apoptosis.
- Caspase inhibitors significantly prevented accelerated neuronal death in Ts16 cultures.
- In the presence of caspase inhibitors, Ts16 neuron survival rates were comparable to control neurons.
Conclusions:
- Accelerated neuronal death in Ts16 mice occurs via caspase-mediated apoptosis.
- Overexpression of genes on mouse chromosome 16 likely contributes to this apoptotic pathway.
- These findings enhance understanding of Down syndrome and Alzheimer's disease pathogenesis.
