title: Hippocampal dysregulation of synaptic plasticity-associated proteins with age-related cognitive decline.
abstract: Age-related cognitive decline occurs without frank neurodegeneration and is the most common cause of memory impairment in aging individuals. With increasing longevity, cognitive deficits, especially in hippocampus-dependent memory processes, are increasing in prevalence. Nevertheless, the neurobiological basis of age-related cognitive decline remains unknown. While concerted efforts have led to the identification of neurobiological changes with aging, few age-related alterations have been definitively correlated to behavioral measures of cognitive decline. In this work, adult (12 months) and aged (28 months) rats were categorized by Morris water maze performance as Adult cognitively Intact, Aged cognitively Intact or Aged cognitively Impaired, and protein expression was examined in hippocampal synaptosome preparations. Previously described differences in synaptic expression of neurotransmission-associated proteins (Dnm1, Hpca, Stx1, Syn1, Syn2, Syp, SNAP25, VAMP2 and 14-3-3 eta, gamma, and zeta) were confirmed between Adult and Aged rats, with no further dysregulation associated with cognitive impairment. Proteins related to synaptic structural stability (MAP2, drebrin, Nogo-A) and activity-dependent signaling (PSD-95, 14-3-3θ, CaMKIIα) were up- and down-regulated, respectively, with cognitive impairment but were not altered with increasing age. Localization of MAP2, PSD-95, and CaMKIIα demonstrated protein expression alterations throughout the hippocampus. The altered expression of activity- and structural stability-associated proteins suggests that impaired synaptic plasticity is a distinct phenomenon that occurs with age-related cognitive decline, and demonstrates that cognitive decline is not simply an exacerbation of the aging phenotype.
authors: Penn State College of Medicine, Department of Pharmacology, Hershey Center for Applied Research, 500 University Drive, Hershey, PA 17033, USA.
authors: Heather D
authors: HD
authors: VanGuilder
authors: Julie A
authors: JA
authors: Farley
authors: Han
authors: H
authors: Yan
authors: Colleen A
authors: CA
authors: Van Kirk
authors: Matthew
authors: M
authors: Mitschelen
authors: William E
authors: WE
authors: Sonntag
authors: Willard M
authors: WM
authors: Freeman
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008569:Memory Disorders / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D013574:Synaptosomes / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins