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The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer’s Disease-like Pathology

It has been suggested that functional traits of the adult brain—all of which are established early in life—may affect the brain’s susceptibility to Alzheimer’s disease (AD). Results of our previous studies on senescence-accelerated OXYS rats, a model of sporadic AD, support this hypothesis. Here, to...

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Autores principales: Stefanova, Natalia A., Kolosova, Nataliya G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865438/
https://www.ncbi.nlm.nih.gov/pubmed/36674977
http://dx.doi.org/10.3390/ijms24021462
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author Stefanova, Natalia A.
Kolosova, Nataliya G.
author_facet Stefanova, Natalia A.
Kolosova, Nataliya G.
author_sort Stefanova, Natalia A.
collection PubMed
description It has been suggested that functional traits of the adult brain—all of which are established early in life—may affect the brain’s susceptibility to Alzheimer’s disease (AD). Results of our previous studies on senescence-accelerated OXYS rats, a model of sporadic AD, support this hypothesis. Here, to elucidate the molecular genetic nature of the aberrations revealed during brain maturation, we analyzed transcriptomes (RNA-seq data) of the prefrontal cortex (PFC) and hippocampus of OXYS rats and Wistar (control) rats in the period of brain maturation critical for OXYS rats (ages P3 and P10; P: postnatal day). We found more than 1000 differentially expressed genes in both brain structures; functional analysis indicated reduced efficiency of the formation of neuronal contacts, presumably explained mainly by deficits of mitochondrial functions. Next, we compared differentially expressed genes in the rat PFC and hippocampus from infancy to the progressive stage of AD-like pathology (five ages in total). Three genes (Thoc3, Exosc8, and Smpd4) showed overexpression in both brain regions of OXYS rats throughout the lifespan. Thus, reduced efficiency of the formation of neural networks in the brain of OXYS rats in infancy likely contributes to the development of their AD-like pathology.
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spelling pubmed-98654382023-01-22 The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer’s Disease-like Pathology Stefanova, Natalia A. Kolosova, Nataliya G. Int J Mol Sci Article It has been suggested that functional traits of the adult brain—all of which are established early in life—may affect the brain’s susceptibility to Alzheimer’s disease (AD). Results of our previous studies on senescence-accelerated OXYS rats, a model of sporadic AD, support this hypothesis. Here, to elucidate the molecular genetic nature of the aberrations revealed during brain maturation, we analyzed transcriptomes (RNA-seq data) of the prefrontal cortex (PFC) and hippocampus of OXYS rats and Wistar (control) rats in the period of brain maturation critical for OXYS rats (ages P3 and P10; P: postnatal day). We found more than 1000 differentially expressed genes in both brain structures; functional analysis indicated reduced efficiency of the formation of neuronal contacts, presumably explained mainly by deficits of mitochondrial functions. Next, we compared differentially expressed genes in the rat PFC and hippocampus from infancy to the progressive stage of AD-like pathology (five ages in total). Three genes (Thoc3, Exosc8, and Smpd4) showed overexpression in both brain regions of OXYS rats throughout the lifespan. Thus, reduced efficiency of the formation of neural networks in the brain of OXYS rats in infancy likely contributes to the development of their AD-like pathology. MDPI 2023-01-11 /pmc/articles/PMC9865438/ /pubmed/36674977 http://dx.doi.org/10.3390/ijms24021462 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Stefanova, Natalia A.
Kolosova, Nataliya G.
The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer’s Disease-like Pathology
title The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer’s Disease-like Pathology
title_full The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer’s Disease-like Pathology
title_fullStr The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer’s Disease-like Pathology
title_full_unstemmed The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer’s Disease-like Pathology
title_short The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer’s Disease-like Pathology
title_sort rat brain transcriptome: from infancy to aging and sporadic alzheimer’s disease-like pathology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865438/
https://www.ncbi.nlm.nih.gov/pubmed/36674977
http://dx.doi.org/10.3390/ijms24021462
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