title: A framework to understand the variations of PSD-95 expression in brain aging and in Alzheimer's disease.
abstract: The postsynaptic density protein PSD-95 is a major element of synapses. PSD-95 is involved in aging, Alzheimer's disease (AD) and numerous psychiatric disorders. However, contradictory data about PSD-95 expression in aging and AD have been reported. Indeed in AD versus control brains PSD-95 varies according to regions, increasing in the frontal cortex, at least in a primary stage, and decreasing in the temporal cortex. In contrast, in transgenic mouse models of aging and AD PSD-95 expression is decreased, in behaviorally aged impaired versus unimpaired rodents it can decrease or increase and finally, it is increased in rodents grown in enriched environments. Different factors explain these contradictory results in both animals and humans, among others concomitant psychiatric endophenotypes, such as depression. The possible involvement of PSD-95 in reactive and/or compensatory mechanisms during AD progression is underscored, at least before the occurrence of important synaptic elimination. Thus, in AD but not in AD transgenic mice, enhanced expression might precede the diminution commonly observed in advanced aging. A two-compartments cell model, separating events taking place in cell bodies and synapses, is presented. Overall these data suggest that AD research will progress by untangling pathological from protective events, a prerequisite for effective therapeutic strategies.
authors.affiliation: Department of Psychiatry, University Hospital of Geneva, 10 chemin du Petit Bel-Air, CH-1225 Geneva, Switzerland; Geneva Neuroscience Center, Geneva University, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland. Electronic address: armand.savioz@hcuge.ch.
authors.forename: Armand
authors.initials: A
authors.lastname: Savioz
authors.affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV, CH-1008 Lausanne, Switzerland.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Leuba
authors.affiliation: Department of Psychiatry, University Hospital of Geneva, 10 chemin du Petit Bel-Air, CH-1225 Geneva, Switzerland.
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Vallet
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000076122:Disks Large Homolog 4 Protein; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008822:Mice, Transgenic; D008954:Models, Biological; D010641:Phenotype
chemical_list: C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins
keywords: Aging; Alzheimer's disease; Depression; Environmental enrichment; PSD-95; Transgenic mice models