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Updated: Jan 3, 2026
Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition
Published on: November 14, 2013
Metabolic Regulation of Hippocampal Neuroprogenitor Apoptosis After Irradiation
Yu-Qing Li1, Marianne Koritzinsky2,3, C Shun Wong1,3
1From the Sunnybrook Health Sciences Centre.
Abstract:
The tumor suppressor p53 is an important regulator of cell fate response after DNA damage. Cell fate response following metabolic stresses has also been linked to p53-dependent pathways. In this study, we asked if 5'-adenosine monophosphate-activated protein kinase (AMPK), the master sensor of cellular energy balance, played a role in p53-dependent apoptosis of neural progenitor cells (NPCs) in the hippocampus after irradiation. Adult mice with targeted disruption of p53 or prkaa2 (gene that encodes AMPKα) in the brain were used to determine the role of p53 and AMPK, respectively, in radiation-induced apoptosis of NPCs in the hippocampus. The p53-dependent apoptosis of NPCs was associated with an increase in phospho-AMPK expression in the dentate gyrus at 8 hours after irradiation. Activation of AMPK was seen in granule neurons and subgranular NPCs. Compared with wildtype mice, apoptosis of NPCs was significantly attenuated in AMPK deficient (nestinCre: prkaa2fl/fl) mice after irradiation. AMPK deficiency did not however alter p53 activation in NPCs after irradiation. We conclude that AMPK may regulate apoptosis of hippocampal NPCs after irradiation. These findings suggest that cellular metabolism may play a role in determining cell fate response such as apoptosis after DNA damage in NPCs.
Insights
AMPK activation regulates p53-dependent apoptosis in neural progenitor cells (NPCs) after irradiation. AMPK deficiency attenuated NPC apoptosis, suggesting a role for cellular metabolism in DNA damage response.
Area of Science:
- Neuroscience
- Cell Biology
- Metabolism
Background:
- The tumor suppressor p53 is crucial for cell fate decisions following DNA damage.
- Cell fate responses to metabolic stress are also linked to p53 pathways.
- The role of 5'-adenosine monophosphate-activated protein kinase (AMPK) in p53-dependent apoptosis of neural progenitor cells (NPCs) after irradiation is unclear.
Purpose of the Study:
- To investigate the role of AMPK in p53-dependent apoptosis of hippocampal NPCs after irradiation.
- To determine if AMPK influences radiation-induced NPC apoptosis in the hippocampus.
Main Methods:
- Utilized adult mice with targeted disruption of p53 or the AMPKα-encoding gene (prkaa2) in the brain.
- Examined radiation-induced apoptosis of NPCs in the hippocampus.
- Assessed p53 activation and AMPK expression (phospho-AMPK) in NPCs post-irradiation.
Main Results:
- p53-dependent NPC apoptosis correlated with increased phospho-AMPK in the dentate gyrus 8 hours after irradiation.
- AMPK activation was observed in granule neurons and subgranular NPCs.
- NPC apoptosis was significantly reduced in AMPK-deficient mice compared to wildtype.
- AMPK deficiency did not affect p53 activation in NPCs following irradiation.
Conclusions:
- AMPK activation appears to regulate apoptosis of hippocampal NPCs after irradiation.
- Cellular metabolism may influence cell fate responses, including apoptosis, after DNA damage in NPCs.
