Abstract
Similar to humans, the normal aged rat population is not homogeneous in terms of cognitive function. Two distinct subpopulations of aged Sprague–Dawley rats can be identified on the basis of spatial memory performance in the hole-board paradigm. It was the aim of the study to reveal protein changes relevant to aging and spatial memory performance. Aged impaired (AI) and unimpaired (AU) male rats, 22–24 months old were selected from a large cohort of 160 animals; young animals served as control. Enriched synaptosomal fractions from dentate gyrus from behaviorally characterized old animals were used for isobaric tags labeling based quantitative proteomic analysis. As differences in peroxiredoxin 6 (PRDX6) levels were a pronounced finding, PRDX6 levels were also quantified by immunoblotting. AI showed impaired spatial memory abilities while AU performed comparably to young animals. Our study demonstrates substantial quantitative alteration of proteins involved in energy metabolism, inflammation and synaptic plasticity during aging. Moreover, we identified protein changes specifically coupled to memory performance of aged rats. PRDX6 levels clearly differentiated AI from AU and levels in AU were comparable to those of young animals. In addition, it was observed that stochasticity in protein levels increased with age and discriminate between AI and AU groups. Moreover, there was a significantly higher variability of protein levels in AI. PRDX6 is a member of the PRDX family and well-defined as a cystein-1 PRDX that reduces and detoxifies hydroxyperoxides. It is well-known and documented that the aging brain shows increased active oxygen species but so far no study proposed a potential target with antioxidant activity that would discriminate between impaired and unimpaired memory performers. Current data, representing so far the largest proteomics data set in aging dentate gyrus (DG), provide the first evidence for a probable role of PRDX6 in memory performance.
Highlights
Cognitive abilities such as memory may see a decline in older adults, there is a notable heterogeneity in cognitive functions across aged subjects
Cognitive decline is often viewed as a natural part of the aging process in humans and animals, there is a notable heterogeneity in cognitive abilities in ‘‘healthy’’ aging (Gallagher and Rapp, 1997; Gallagher et al, 2006; Gerstein et al, 2013)
Lasting reference memory formed by learning on the hole-board has been related to hippocampal long-term potentiation and it has been shown in several studies that the dentate gyrus (DG) is involved (Uzakov et al, 2005; Korz and Frey, 2007; Woldeit and Korz, 2010)
Summary
Cognitive abilities such as memory may see a decline in older adults, there is a notable heterogeneity in cognitive functions across aged subjects. Any aged rat population can be distinguished into two subpopulations: impaired (AI) and unimpaired (AU) in spatial learning and memory tasks (Brouillette and Quirion, 2008; Menard and Quirion, 2012; Farso et al, 2013). According to the free radical theory of aging, mitochondria initiate most of the deleterious changes in aging. Mitochondria are the main producers of energy in the cells and the principal source of intracellular reactive oxygen species (ROS). Mitochondrial dysfunction and reduced expression and/or activity of naturally occurring antioxidants seems to be critically involved in both, normal and pathological aging, as well as neurodegenerative disorders
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