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PPAR-δ Activation Ameliorates Diabetes-Induced Cognitive Dysfunction by Modulating Integrin-linked Kinase and AMPA Receptor Function
E.A. Abdel-Rahman, S. Bhattacharya, M. Buabeid, , M. Majrashi, J. Bloemer, Y.-X. Tao, M. Dhanasekaran, M. Escobar, R. AminShow More
Published in Taylor and Francis
2019
PMID: 31008686
Volume: 38
   
Issue: 8
Pages: 693 - 702
Abstract
An estimated 9% of the American population experiences type II diabetes mellitus (T2DM) due to diet or genetic predisposition. Recent reports indicate that patients with T2DM are at increased risk for cognitive dysfunctions, as observed in conditions like Alzheimer’s disease (AD). In addition, AD is the leading cause of dementia, highlighting the urgency of developing novel therapeutic targets for T2DM-induced cognitive deficits. The peroxisome proliferator activated receptor-δ (PPAR-δ) is highly expressed in the brain and has been shown to play an important role in spatial memory and hippocampal neurogenesis. However, the effect of PPAR-δ agonists on T2DM-induced cognitive impairment has not been explored. In this study, the effects of GW0742 (a selective PPAR-δ agonist) on hippocampal synaptic transmission, plasticity, and spatial memory were investigated in the db/db mouse model of T2DM. Oral administration of GW0742 for 2 weeks significantly improved hippocampal long-term potentiation. In addition, GW0742 effectively prevented deficits in hippocampal dependent spatial memory in db/db mice. PPAR-δ–mediated improvements in synaptic plasticity and behavior were accompanied by a significant recovery in hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor–mediated synaptic transmission. Our findings suggest that activation of PPAR-δ might ameliorate T2DM-induced impairments in hippocampal synaptic plasticity and memory. © 2019, © 2019 American College of Nutrition.
About the journal
JournalData powered by TypesetJournal of the American College of Nutrition
PublisherData powered by TypesetTaylor and Francis
ISSN7315724
Open AccessNo
Concepts (6)
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    Cognitive impairment
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    Diabetes mellitus
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    GW0742
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    Integrin-linked kinase
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    Neuroprotection
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    Peroxisome proliferator activated receptor