title: Rosiglitazone induces mitochondrial biogenesis in mouse brain.
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.
authors.affiliation: Department of Quantitative Expression, Division of Genetics Research, GlaxoSmithKline, Research Triangle Park, NC 27278, USA. Jay.C.Strum@gsk.com
authors.forename: Jay C
authors.initials: JC
authors.lastname: Strum
authors.forename: Ron
authors.initials: R
authors.lastname: Shehee
authors.forename: David
authors.initials: D
authors.lastname: Virley
authors.forename: Jill
authors.initials: J
authors.lastname: Richardson
authors.forename: Michael
authors.initials: M
authors.lastname: Mattie
authors.forename: Paula
authors.initials: P
authors.lastname: Selley
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
authors.forename: Christina
authors.initials: C
authors.lastname: Nock
authors.forename: Ann
authors.initials: A
authors.lastname: Saunders
authors.forename: Allen
authors.initials: A
authors.lastname: Roses
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D053318:Apolipoprotein E3 / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics*; D005625:Frontal Lobe / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects*; D001678:Organelle Biogenesis; D047495:PPAR gamma / Q000819:agonists; D012333:RNA, Messenger / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004272:DNA, Mitochondrial; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D000097983:ERRalpha Estrogen-Related Receptor