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Aged SOD overexpressing mice exhibit enhanced spatial memory while lacking hippocampal neurogenesis
Ariel Kamsler1, Avi Avital, Varda Greenberger
1Department of Neurobiology, The Weizmann Institute, Rehovot, Israel. kamsler@mit.edu
Antioxidants & Redox Signaling
|November 23, 2006
Summary
Superoxide dismutase (SOD) gene overexpression in aged mice improved spatial learning and memory. This suggests that increased hydrogen peroxide (H2O2) production benefits cognitive function in aging mice.
Area of Science:
- Neuroscience
- Aging Research
- Molecular Biology
Background:
- Reactive oxygen species (ROS) play a role in aging and cognitive decline.
- Superoxide dismutase (SOD) is an enzyme that neutralizes ROS.
- Previous studies suggested a link between SOD and hippocampal function in aged mice.
Purpose of the Study:
- To investigate the impact of SOD gene overexpression on learning and memory in aged mice.
- To explore the relationship between adult neurogenesis and spatial learning in young and aged mice.
- To determine if increased hydrogen peroxide (H2O2) production is beneficial for cognitive function in aging.
Main Methods:
- Comparison of hippocampal slices from aged wild-type (wt) and SOD-overexpressing mice for long-term potentiation (LTP).
- Assessment of spatial learning and memory using a water maze task in young-adult and aged wt and SOD transgenic mice.
- Quantification of adult neurogenesis by counting doublecortin-labeled new dentate gyrus neurons.
Main Results:
- Aged mice overexpressing SOD showed significantly larger LTP compared to aged wt mice.
- Aged wt and SOD mice exhibited a 90% reduction in new dentate gyrus neurons compared to young mice, with no genotypic difference.
- Aged SOD mice demonstrated superior performance in both reference and working memory tasks in the water maze compared to aged wt controls.
Conclusions:
- Overexpression of the SOD gene enhances cognitive function, specifically spatial learning and memory, in aged mice.
- Increased hydrogen peroxide (H2O2) production, a byproduct of SOD activity, appears beneficial for cognitive performance in aging.
- While adult neurogenesis is reduced in aged mice, SOD-mediated mechanisms can still improve cognitive function.

