Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

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Lipids play a major role for several brain functions, including cognition and memory. There is a series of work on individual lipids showing involvement in memory mechanisms, a concise lipidome was not reported so far. Moreover, there is no evidence for age-related memory decline and there is only work on brain of young vs. aging animals. Aging animals, however, are not a homogeneous group with respect to memory impairments, thus animals with impaired and unimpaired memory can be discriminated. Following recent studies of hippocampal lipid profiles and hypothalamus controlled hormone profiles, the aim of this study was to compare hypothalamic, lipidomic changes in male Sprague-Dawley rats between young (YM), old impaired (OMI) and old unimpaired (OMU) males. Grouping criterions for aged rats were evaluated by testing them in a spatial memory task, the hole-board. YMs were also tested. Subsequently brains were removed, dissected and hypothalami were kept at −80 • C until sample preparation and analysis on liquid chromatography / mass spectrometry (LC-MS). Significant differences in the amounts of a series of lipids from several classes could be detected between young and aged and between OMI and OMU. A large number of lipids were increased in OMI and a smaller number in OMU as compared to young rats. Differences of lipid ratios (log2 of ratio) between OMI and OMU consisted of glycerophosphocholines (

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differences in Hypothalamic Lipid Profiles of Young and Aged Male Rats With Impaired and Unimpaired Spatial Cognitive Abilities and Memory

Wackerlig

Köfeler

Korz

et al. 2020

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“…A hole-board test was performed as previously described with minor modifications (Smidak et al, 2017). The hole-board with the dimension of 1 m × 1 m was manufactured of a black plastic board bounded by a translucent plexiglass wall, with proximal spatial cues (black/white symbols) and surrounded by room structures which served as distal cues.…”

Section: Methodsmentioning

confidence: 99%

“…The pooled-labeled sample was separated using the Pierce TM High pH Reversed-Phase Peptide Fractionation Kit (Thermo Scientific) into eight fractions and each fraction was reconstituted in 50 μL of 5% formic acid. The peptide fractions were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as described previously (Smidak et al, 2017) with two technical replicates per sample and 5 μL injection volume. MS raw data were searched against UniProtKB Rattus norvegicus complete proteome database (UP000002494, 31571 sequences, downloaded on February 11th, 2018) using MASCOT 2.4 (MatrixScience) through Proteome Discoverer 2.1 platform (Thermo Scientific) as previously published (Smidak et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

Dentate Gyrus Peroxiredoxin 6 Levels Discriminate Aged Unimpaired From Impaired Rats in a Spatial Memory Task

Lubec

Šmidák

Maliković

et al. 2019

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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.

“…This number was chosen because animals with 40 hole visits have the chance to find all four pellets during each of the 10 trials. This ensures that behavioral performance is related to cognition and not motoric activity ( Smidak et al, 2017 ; Kristofova et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Moderate Differences in Feeding Diets Largely Affect Motivation and Spatial Cognition in Adult and Aged but Less in Young Male Rats

Maliković

Feyissa

Hussein

et al. 2018

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Nutrition can have significant effects on behavior and cognitive processes. Most of the studies related to this use extremely modified diets, such as high fat contents or the exclusion of distinct components needed for normal development and bodily homeostasis. Here we report significant effects of diets with moderate differences in compositions on food rewarded spatial learning in young (3–4 months), adult (6–7 months), and aged (17–18 months) rats. Young rats fed with a lower energy diet showed better performance only during aquisition of the spatial task when compared to rats fed with a standard diet. Adult rats (6–7 months) fed with a standard diet performed less well in the spatial learning task, than rats fed with lower energy diet. Aged rats fed with a lower energy diet (from 13 to 18 months of age) performed better during all training phases, as in a previous test when they were adult and fed with a standard diet. This difference could only be partly explained by lower motivation to search for food in the first test. Correspondingly, the variability of individual performance was significantly higher and increased over trials in adult rats fed with the standard diet as compared to adult rats fed with lower energy diet. Thus, moderate changes in feeding diets have large effects on motivation and cognition in elderly and less in young rats in a food rewarded spatial learning task. Therefore, nutrition effects upon food rewarded spatial learning and memory should be considered especially in aging studies.