title: Integrative Transcriptome Profiling of Cognitive Aging and Its Preservation through Ser/Thr Protein Phosphatase Regulation.
abstract: Environmental enrichment has been reported to delay or restore age-related cognitive deficits, however, a mechanism to account for the cause and progression of normal cognitive decline and its preservation by environmental enrichment is lacking. Using genome-wide SAGE-Seq, we provide a global assessment of differentially expressed genes altered with age and environmental enrichment in the hippocampus. Qualitative and quantitative proteomics in naïve young and aged mice was used to further identify phosphorylated proteins differentially expressed with age. We found that increased expression of endogenous protein phosphatase-1 inhibitors in aged mice may be characteristic of long-term environmental enrichment and improved cognitive status. As such, hippocampus-dependent performances in spatial, recognition, and associative memories, which are sensitive to aging, were preserved by environmental enrichment and accompanied by decreased protein phosphatase activity. Age-associated phosphorylated proteins were also found to correspond to the functional categories of age-associated genes identified through transcriptome analysis. Together, this study provides a comprehensive map of the transcriptome and proteome in the aging brain, and elucidates endogenous protein phosphatase-1 inhibition as a potential means through which environmental enrichment may ameliorate age-related cognitive deficits.
authors.affiliation: Brain Research Institute, Medical Faculty of the University of Zürich and Department of Health Science and Technology ETH Zürich, Zürich, Switzerland.
authors.forename: C Sehwan
authors.initials: CS
authors.lastname: Park
authors.affiliation: Brain Research Institute, Medical Faculty of the University of Zürich and Department of Health Science and Technology ETH Zürich, Zürich, Switzerland; Institute of Pharmacology and Toxicology, Human Sleep Psychopharmacology, University of Zürich, Zürich, Switzerland.
authors.forename: Amandine
authors.initials: A
authors.lastname: Valomon
authors.affiliation: Institute of Anatomy, Neuroanatomy and Behavior, University of Zürich, Zürich, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Welzl
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001245:Association Learning / Q000502:physiology; D003071:Cognition; D003072:Cognition Disorders / Q000517:prevention & control*; D004779:Environment Design; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006624:Hippocampus / Q000737:chemistry / Q000201:enzymology / Q000502:physiology*; D006799:Housing, Animal; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D010988:Play and Playthings; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D021641:Recognition, Psychology / Q000502:physiology; D016415:Sequence Alignment; D059467:Transcriptome
chemical_list: D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D054645:Protein Phosphatase 1