Dataset Information

Intraneuronal Amyloid Beta Accumulation Disrupts Hippocampal CRTC1-Dependent Gene Expression and Cognitive Function in a Rat Model of Alzheimer Disease.

ABSTRACT: In Alzheimer disease (AD), the accumulation of amyloid beta (Aβ) begins decades before cognitive symptoms and progresses from intraneuronal material to extracellular plaques. To date, however, the precise mechanism by which the early buildup of Aβ peptides leads to cognitive dysfunction remains unknown. Here, we investigate the impact of the early Aβ accumulation on temporal and frontal lobe dysfunction. We compared the performance of McGill-R-Thy1-APP transgenic AD rats with wild-type littermate controls on a visual discrimination task using a touchscreen operant platform. Subsequently, we conducted studies to establish the biochemical and molecular basis for the behavioral alterations. It was found that the presence of intraneuronal Aβ caused a severe associative learning deficit in the AD rats. This coincided with reduced nuclear translocation and genomic occupancy of the CREB co-activator, CRTC1, and decreased production of synaptic plasticity-associated transcripts Arc, c-fos, Egr1, and Bdnf. Thus, blockade of CRTC1-dependent gene expression in the early, preplaque phase of AD-like pathology provides a molecular basis for the cognitive deficits that figure so prominently in early AD.

SUBMITTER: Wilson EN

PROVIDER: S-EPMC5378482 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Intraneuronal Amyloid Beta Accumulation Disrupts Hippocampal CRTC1-Dependent Gene Expression and Cognitive Function in a Rat Model of Alzheimer Disease.

Wilson Edward N EN Abela Andrew R AR Do Carmo Sonia S Allard Simon S Marks Adam R AR Welikovitch Lindsay A LA Ducatenzeiler Adriana A Chudasama Yogita Y Cuello A Claudio AC

Cerebral cortex (New York, N.Y. : 1991) 20170201 2

In Alzheimer disease (AD), the accumulation of amyloid beta (Aβ) begins decades before cognitive symptoms and progresses from intraneuronal material to extracellular plaques. To date, however, the precise mechanism by which the early buildup of Aβ peptides leads to cognitive dysfunction remains unknown. Here, we investigate the impact of the early Aβ accumulation on temporal and frontal lobe dysfunction. We compared the performance of McGill-R-Thy1-APP transgenic AD rats with wild-type littermat ...[more]

PMID: 26759481

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Project description:The prevention or delay of brain senescence would enhance the quality of life for older persons. We investigated the effects of soybean extracts in senescence-accelerated (SAMP10) mice. This mouse is a model of brain senescence with a short life span, cerebral atrophy and cognitive dysfunction. Mice were fed a diet containing soybean extracts from 1 to 12 months of age. The effects of green and yellow soybean extracts were compared with a control diet without soybean extracts. Cognitive functions were higher in aged mice fed green soybean than age-matched control mice and mice fed yellow soybean. We further investigated transcriptome of the SAMP10 hippocampus indicated that expression levels of 36 genes were significantly higher and 19 genes were lower in mice that ingested green soybean than in mice that ingested yellow soybean. Some of the evidences were reconfirmed by real time PCR analysis; the levels of Cdh1 and Ptgds mRNA were significantly higher and that the level of Aplp1 was significantly lower in aged SAMP10 mice fed green soybean than mice ingested yellow soybean and control mice. Additionally, the amount of amyloid beta 40 and 42 was lower in the insoluble fraction of aged SAMP10 mice fed green soybean than control mice and mice fed yellow soybean, although the levels of amyloid beta 40 and 42 in the soluble fraction were not different. Lipocalin-type prostaglandin D2 synthase (L-PGDS) has been proposed as the endogenous amyloid beta - chaperone, suggesting that amyloid aggregation was lower in mice fed green soybean than control mice and mice fed yellow soybean. These results indicate that the intake of green soybean improved cognitive function in aged mice, and suppressed amyloid beta accumulation. Green soybean might help healthy aging of the brain in older persons. The effect of green and yellow soybean extracts on cognitive function in aged SAMP10 mice. Mice were fed a CE-2 diet containing 3.0% soybean extracts taken from both yellow and green soybean species, from 1 to 12 months of age. Total RNA was extracted from the stored hippocampus for DNA microarray analysis.

Dataset Information

Intraneuronal Amyloid Beta Accumulation Disrupts Hippocampal CRTC1-Dependent Gene Expression and Cognitive Function in a Rat Model of Alzheimer Disease.

Publications

Intraneuronal Amyloid Beta Accumulation Disrupts Hippocampal CRTC1-Dependent Gene Expression and Cognitive Function in a Rat Model of Alzheimer Disease.

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