Abstract
Rosiglitazone was found to simulate mitochondrial biogenesis in mouse brain in an apolipoprotein (Apo) E isozyme-independent manner. Rosiglitazone induced both mitochondrial DNA (mtDNA) and estrogen-stimulated related receptor alpha (ESRRA) mRNA, a key regulator of mitochondrial biogenesis. Transcriptomics and proteomics analysis suggested the mitochondria produced in the presence of human ApoE3 and E4 were not as metabolically efficient as those in the wild type or ApoE knockout mice. Thus, we propose that PPARgamma agonism induces neuronal mitochondrial biogenesis and improves glucose utilization leading to improved cellular function and provides mechanistic support for the improvement in cognition observed in treatment of Alzheimer's patients with rosiglitazone.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / drug therapy
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Animals
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Apolipoprotein E3 / metabolism
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Apolipoprotein E4 / metabolism
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Apolipoproteins E / genetics
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Brain / drug effects*
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Cognition / drug effects
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DNA, Mitochondrial / genetics*
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ERRalpha Estrogen-Related Receptor
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Frontal Lobe / drug effects
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Gene Expression Regulation / drug effects
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Humans
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Hypoglycemic Agents / pharmacology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mitochondria / drug effects*
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Organelle Biogenesis*
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PPAR gamma / agonists
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RNA, Messenger / genetics*
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Receptors, Estrogen / genetics*
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Reverse Transcriptase Polymerase Chain Reaction
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Rosiglitazone
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Thiazolidinediones / pharmacology*
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Thiazolidinediones / therapeutic use
Substances
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Apolipoprotein E3
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Apolipoprotein E4
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Apolipoproteins E
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DNA, Mitochondrial
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Hypoglycemic Agents
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PPAR gamma
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RNA, Messenger
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Receptors, Estrogen
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Thiazolidinediones
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Rosiglitazone