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000285354 1001_ $$aGómez-Pascual, Alicia$$b0
000285354 245__ $$aThe Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus.
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000285354 520__ $$aIn aged humans and mice, hypobranched glycogen aggregates, known as polyglucosan bodies (PGBs), accumulate in hippocampal astrocytes. While PGBs are linked to cognitive decline in neurological diseases, they remain largely unstudied in the context of typical aging. We show that PGBs arise in autophagy-dysregulated astrocytes in the aged hippocampus, with substantial variation among 32 inbred BXD mouse strains. Genetic mapping through quantitative trait locus analysis identified a major locus (Pgb1) that modulates hippocampal PGB burden. Extensive transcriptomic and proteomic datasets were produced for the aged hippocampus of the BXD family to investigate the mechanism by which the Pgb1 locus modulates PGB burden. We identified that Pgb1 contains allelic Smarcal1 and Usp37 variants and influences PGB burden through trans-regulation of mRNA and protein expression levels, including abundance of glycogen-mobilizing factor PYGB. Furthermore, comprehensive phenome-wide association scans, transcriptomic analyses, and direct behavioral testing demonstrated that cognition remains intact despite age-related PGB burden. A record of this paper's transparent peer review process is included in the supplemental information.
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000285354 650_7 $$2Other$$aastrocytes
000285354 650_7 $$2Other$$abrain aging
000285354 650_7 $$2Other$$aglycogen metabolism
000285354 650_7 $$2Other$$ahippocampus
000285354 650_7 $$2Other$$apolyglucosan bodies
000285354 650_7 $$2Other$$aquantitative trait locus analysis
000285354 650_7 $$2Other$$asystem genetics
000285354 650_7 $$09005-79-2$$2NLM Chemicals$$aGlycogen
000285354 650_7 $$09012-72-0$$2NLM Chemicals$$apolyglucosan
000285354 650_7 $$2NLM Chemicals$$aGlucans
000285354 650_2 $$2MeSH$$aAnimals
000285354 650_2 $$2MeSH$$aHippocampus: metabolism
000285354 650_2 $$2MeSH$$aGlycogen: metabolism
000285354 650_2 $$2MeSH$$aMice
000285354 650_2 $$2MeSH$$aAstrocytes: metabolism
000285354 650_2 $$2MeSH$$aAging: genetics
000285354 650_2 $$2MeSH$$aAging: metabolism
000285354 650_2 $$2MeSH$$aMale
000285354 650_2 $$2MeSH$$aQuantitative Trait Loci: genetics
000285354 650_2 $$2MeSH$$aMice, Inbred C57BL
000285354 650_2 $$2MeSH$$aHumans
000285354 650_2 $$2MeSH$$aGlucans
000285354 7001_ $$aGlikman, Dow M$$b1
000285354 7001_ $$aNg, Hui Xin$$b2
000285354 7001_ $$aTomkins, James E$$b3
000285354 7001_ $$aLu, Lu$$b4
000285354 7001_ $$0P:(DE-2719)9001899$$aXu, Ying$$b5
000285354 7001_ $$aAshbrook, David G$$b6
000285354 7001_ $$aKaczorowski, Catherine$$b7
000285354 7001_ $$0P:(DE-2719)2000011$$aKempermann, Gerd$$b8
000285354 7001_ $$aKillmar, John$$b9
000285354 7001_ $$aMozhui, Khyobeni$$b10
000285354 7001_ $$aOhlenschläger, Oliver$$b11
000285354 7001_ $$aAebersold, Rudolf$$b12
000285354 7001_ $$aIngram, Donald K$$b13
000285354 7001_ $$aWilliams, Evan G$$b14
000285354 7001_ $$0P:(DE-2719)2000010$$aJucker, Mathias$$b15
000285354 7001_ $$aOverall, Rupert W$$b16
000285354 7001_ $$aWilliams, Robert W$$b17
000285354 7001_ $$ade Bakker, Dennis E M$$b18
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