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Rosiglitazone improves contextual fear conditioning in aged rats
Carmelina Gemma1, Heather Stellwagen, Matthew Fister
1James A. Haley VA Hospital, 13000 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
Neuroreport
|September 17, 2004
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) show promise for Alzheimer's disease. Rosiglitazone, a PPARgamma agonist, improved memory in aged rats by preventing hippocampal deficits.
Area of Science:
- Neuroscience
- Pharmacology
- Aging Research
Background:
- Non-steroidal anti-inflammatory drugs (NSAIDs) are linked to benefits in Alzheimer's disease and neuroinflammation.
- Peroxisome proliferator-activated receptors (PPARs) are potential targets for NSAID mechanisms.
Purpose of the Study:
- To investigate the effect of rosiglitazone, a PPARgamma agonist, on contextual fear conditioning in aged rats.
- To determine if PPARgamma activation can counteract age-related cognitive decline.
Main Methods:
- Aged rats (20 months old) received rosiglitazone in their diet for two months.
- Behavioral testing assessed contextual fear conditioning, a hippocampal-dependent task.
- Hippocampal tissue was analyzed for interleukin-1beta, oxidative damage markers, and NMDA receptor expression.
Main Results:
- Aged rats treated with rosiglitazone exhibited significantly increased freezing behavior compared to aged control rats.
- This improvement in fear conditioning was comparable to young control rats.
- Rosiglitazone did not alter hippocampal interleukin-1beta levels, oxidative damage markers, or NMDA receptor expression.
Conclusions:
- Activation of PPARgamma by rosiglitazone effectively prevented age-related deficits in hippocampal function.
- This suggests PPARgamma agonists may be a therapeutic strategy for cognitive aging and neurodegenerative diseases.