Related Experiment Video
Updated: Feb 11, 2026
Stimulating and Analyzing Adult Neurogenesis in the Drosophila Central Brain
Published on: October 8, 2021
INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice
Oanh Le1, Lina Palacio2, Gilbert Bernier3
1Centre de Recherche du CHU Ste-Justine, 3175 Côte Sainte-Catherine, Montréal, Québec H3T 1C5, Canada.
Abstract:
Brain neurogenesis is severely impaired following exposure to ionizing radiation (IR). We and others have shown that the expression of the tumor suppressor gene p16INK4a is increased in tissues exposed to IR and thus hypothesized that its expression could limit neurogenesis in the irradiated brain. Here, we found that exposure to IR leads to persistent DNA damage and the expression of p16INK4a in the hippocampus and subventricular zone regions. This was accompanied by a decline in neurogenesis, as determined by doublecortin expression and bromodeoxyuridine incorporation, an effect partially restored in Ink4a/arf-null mice. Increased neurogenesis in the absence of INK4a/ARF expression was independent of apoptosis and activation of the microglia. Moreover, treatment of irradiated mice with a superoxide dismutase mimetic or clearance of p16INK4a-expressing cells using mouse genetics failed to increase neurogenesis. In conclusion, our results suggest that IR-induced p16INK4a expression is a mechanism that limits neurogenesis.
Insights
Ionizing radiation (IR) impairs brain neurogenesis. Our study reveals that increased p16INK4a gene expression after IR exposure limits this crucial process, particularly in the hippocampus.
Area of Science:
- Neuroscience
- Molecular Biology
- Radiation Biology
Background:
- Brain neurogenesis is vital for cognitive function.
- Ionizing radiation (IR) exposure significantly disrupts neurogenesis.
- The tumor suppressor gene p16INK4a is upregulated in IR-exposed tissues.
Purpose of the Study:
- To investigate the role of p16INK4a in IR-induced neurogenesis impairment.
- To determine if p16INK4a expression limits neurogenesis in the irradiated brain.
Main Methods:
- Exposure of mice to ionizing radiation.
- Assessing DNA damage and p16INK4a expression in the hippocampus and subventricular zone.
- Measuring neurogenesis using doublecortin expression and bromodeoxyuridine incorporation.
- Utilizing Ink4a/arf-null mice to evaluate the role of INK4a/ARF.
Main Results:
- IR exposure caused persistent DNA damage and elevated p16INK4a expression.
- Neurogenesis declined post-IR, an effect partially rescued in Ink4a/arf-null mice.
- Increased neurogenesis in INK4a/ARF-deficient mice was independent of apoptosis and microglial activation.
Conclusions:
- IR-induced p16INK4a expression is a key mechanism limiting neurogenesis.
- Targeting p16INK4a may offer therapeutic potential for radiation-induced brain damage.
Related Concept Videos
01:15Neurogenesis and Regeneration of Nervous Tissue
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:42What is Gene Expression?
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
01:36What is Gene Expression?
01:58Cell Specific Gene Expression
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment