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Late enrichment maintains accurate recent and remote spatial memory only in aged rats that were unimpaired when middle aged.

ABSTRACT: Exposure of rodents to a stimulating environment has beneficial effects on some cognitive functions that are impaired during physiological aging, and especially spatial reference memory. The present study investigated whether environmental enrichment rescues these functions in already declining subjects and/or protects them from subsequent decline. Subgroups of 17-mo-old female rats with unimpaired versus impaired performance in a spatial reference memory task (Morris water maze) were housed until the age of 24 mo in standard or enriched environment. They were then trained in a second reference memory task, conducted in a different room than the first, and recent (1 d) and remote (10 d) memory were assessed. In unimpaired subgroups, spatial memory declined from 17 to 24 mo in rats housed in standard conditions; an enriched environment during this period allowed maintenance of accurate recent and remote spatial memory. At 24 mo, rats impaired at the age of 17 mo housed in enriched environment learned the task and displayed substantial recent memory, but their performance remained lower than that of unimpaired rats, showing that enrichment failed to rescue spatial memory in already cognitively declining rats. Controls indicated carryover effects of the first water maze training, especially in aged rats housed in standard condition, and confirmed the beneficial effect of enrichment on remote memory of aged rats even if they performed poorly than young adults housed for the same duration in standard or enriched condition.

SUBMITTER: Fuchs F

PROVIDER: S-EPMC4880144 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Late enrichment maintains accurate recent and remote spatial memory only in aged rats that were unimpaired when middle aged.

Fuchs Fanny F Herbeaux Karine K Aufrere Noémie N Kelche Christian C Mathis Chantal C Barbelivien Alexandra A Majchrzak Monique M

Learning & memory (Cold Spring Harbor, N.Y.) 20160518 6

Exposure of rodents to a stimulating environment has beneficial effects on some cognitive functions that are impaired during physiological aging, and especially spatial reference memory. The present study investigated whether environmental enrichment rescues these functions in already declining subjects and/or protects them from subsequent decline. Subgroups of 17-mo-old female rats with unimpaired versus impaired performance in a spatial reference memory task (Morris water maze) were housed unt ...[more]

PMID: 27194797

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Project description: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.

Project description:PurposeTo determine whether the APOE-ε4 allele modulates the relationship between regional β-amyloid (Aβ) accumulation and cognitive change in middle-aged cognitively unimpaired (CU) participants.MethodsThe 352 CU participants (mean aged 61.1 [4.7] years) included completed two cognitive assessments (average interval 3.34 years), underwent [18F]flutemetamol Aβ positron emission tomography (PET), T1w magnetic resonance imaging (MRI), as well as APOE genotyping. Global and regional Aβ PET positivity was assessed across five regions-of-interest by visual reading (VR) and regional Centiloids. Linear regression models were developed to examine the interaction between regional and global Aβ PET positivity and APOE-ε4 status on longitudinal cognitive change assessed with the Preclinical Alzheimer's Cognitive Composite (PACC), episodic memory, and executive function, after controlling for age, sex, education, cognitive baseline scores, and hippocampal volume.ResultsIn total, 57 participants (16.2%) were VR+ of whom 41 (71.9%) were APOE-ε4 carriers. No significant APOE-ε4*global Aβ PET interactions were associated with cognitive change for any cognitive test. However, APOE-ε4 carriers who were VR+ in temporal areas (n = 19 [9.81%], p = 0.04) and in the striatum (n = 8 [4.14%], p = 0.01) exhibited a higher decline in the PACC. The temporal areas findings were replicated when regional PET positivity was determined with Centiloid values. Regionally, VR+ in the striatum was associated with higher memory decline. As for executive function, interactions between APOE-ε4 and regional VR+ were found in temporal and parietal regions, and in the striatum.ConclusionCU APOE-ε4 carriers with a positive Aβ PET VR in regions known to accumulate amyloid at later stages of the Alzheimer's disease (AD) continuum exhibited a steeper cognitive decline. This work supports the contention that regional VR of Aβ PET might convey prognostic information about future cognitive decline in individuals at higher risk of developing AD.Clinicaltrialsgov Identifier: NCT02485730. Registered 20 June 2015 https://clinicaltrials.gov/ct2/show/NCT02485730 and ClinicalTrials.gov Identifier:NCT02685969. Registered 19 February 2016 https://clinicaltrials.gov/ct2/show/NCT02685969 .

Dataset Information

Late enrichment maintains accurate recent and remote spatial memory only in aged rats that were unimpaired when middle aged.

Publications

Late enrichment maintains accurate recent and remote spatial memory only in aged rats that were unimpaired when middle aged.

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