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A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
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PPAR-δ Activation Ameliorates Diabetes-Induced Cognitive Dysfunction by Modulating Integrin-linked Kinase and AMPA
Engy A Abdel-Rahman1,2, Subhrajit Bhattacharya3, Manal Buabeid1,4
1Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA.
Journal of the American College of Nutrition
|April 23, 2019
Summary
Type II diabetes mellitus (T2DM) increases Alzheimer's disease risk. PPAR-δ activation with GW0742 improved memory and synaptic function in a T2DM mouse model, suggesting a new therapeutic target.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Pharmacology
Background:
- Type II Diabetes Mellitus (T2DM) is linked to cognitive decline and Alzheimer's Disease (AD).
- Peroxisome proliferator activated receptor-δ (PPAR-δ) plays a role in brain functions like memory and neurogenesis.
- The therapeutic potential of PPAR-δ agonists for T2DM-related cognitive impairment remains unexplored.
Purpose of the Study:
- To investigate the effects of the PPAR-δ agonist GW0742 on cognitive function in a mouse model of T2DM.
- To examine GW0742's impact on hippocampal synaptic transmission and plasticity.
Main Methods:
- Utilized the db/db mouse model, a standard model for T2DM.
- Administered GW0742 orally for two weeks.
- Assessed hippocampal long-term potentiation, spatial memory, and synaptic transmission.
Main Results:
- GW0742 treatment significantly enhanced hippocampal long-term potentiation.
- GW0742 prevented spatial memory deficits in db/db mice.
- Improvements in synaptic plasticity and memory correlated with restored AMPA receptor function.
Conclusions:
- Activation of PPAR-δ with GW0742 ameliorates T2DM-induced cognitive deficits.
- PPAR-δ activation may be a promising therapeutic strategy for T2DM-related cognitive impairment.
- Targeting PPAR-δ could offer a novel approach to combatting dementia associated with metabolic disorders.
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