Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease development
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease. It produces atrophic changes in the brain, which cause dementia. The incidence of AD is increasing with increasing life expectancy and gradual aging of the population in developed countries. There are no effective prophylacti...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2015-12-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/434 |
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| author | N. A. Stefanova E. E. Korbolina N. I. Ershov E. I. Rogaev N. G. Kolosova |
| author_facet | N. A. Stefanova E. E. Korbolina N. I. Ershov E. I. Rogaev N. G. Kolosova |
| author_sort | N. A. Stefanova |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease. It produces atrophic changes in the brain, which cause dementia. The incidence of AD is increasing with increasing life expectancy and gradual aging of the population in developed countries. There are no effective prophylactic interventions because of insufficient understanding of the AD pathogenesis and the absence of adequate experimental models. Recently, we showed that senescence-accelerated OXYS rats represent a promising model of AD; in these rats, accelerated aging of the brain is accompanied by the typical signs of AD: degenerative alterations and death of neurons, a decrease in synaptic density, mitochondrial dysfunction, hyperphosphorylation of the tau protein, an increased level of amyloid β (Aβ1–42), and the formation of amyloid plaques. To elucidate how these signs develop, we used a nextgeneration RNA sequencing technique (RNA-Seq) to study the prefrontal-cortex transcriptome of OXYS rats during the manifestation of AD signs (at an age of 5 months) and during their active progression (at an age of 18 months), using age-matched Wistar rats (parental strain) as controls. At the age of 5 months, there were significant differences between OXYS and Wistar rats (p < 0.01) in the mRNA expression of more than 900 genes (> 2000 genes at the age of 18 months) in the prefrontal cortex. Most of these genes were related to neuronal plasticity, protein phosphorylation, Са2+ homeostasis, hypoxia, immune processes, and apoptosis. Between the ages of 5 and 18 months, there were changes in the expression of 499 genes in Wistar rats and changes in the expression of 5500 genes in OXYS rats. Only 333 genes were common between these sets. This finding points to differences in the mechanisms and rates of age-related changes in the brain between normal aging and the period of development of AD-specific neurodegenerative processes. |
| format | Article |
| id | doaj-art-4c40d35563ab4dc8b65072de034a7d64 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2015-12-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-4c40d35563ab4dc8b65072de034a7d642025-02-01T09:58:02ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592015-12-0119444545410.18699/VJ15.059392Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease developmentN. A. Stefanova0E. E. Korbolina1N. I. Ershov2E. I. Rogaev3N. G. Kolosova4Institute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, Russia Novosibirsk State University, Novosibirsk, RussiaAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease. It produces atrophic changes in the brain, which cause dementia. The incidence of AD is increasing with increasing life expectancy and gradual aging of the population in developed countries. There are no effective prophylactic interventions because of insufficient understanding of the AD pathogenesis and the absence of adequate experimental models. Recently, we showed that senescence-accelerated OXYS rats represent a promising model of AD; in these rats, accelerated aging of the brain is accompanied by the typical signs of AD: degenerative alterations and death of neurons, a decrease in synaptic density, mitochondrial dysfunction, hyperphosphorylation of the tau protein, an increased level of amyloid β (Aβ1–42), and the formation of amyloid plaques. To elucidate how these signs develop, we used a nextgeneration RNA sequencing technique (RNA-Seq) to study the prefrontal-cortex transcriptome of OXYS rats during the manifestation of AD signs (at an age of 5 months) and during their active progression (at an age of 18 months), using age-matched Wistar rats (parental strain) as controls. At the age of 5 months, there were significant differences between OXYS and Wistar rats (p < 0.01) in the mRNA expression of more than 900 genes (> 2000 genes at the age of 18 months) in the prefrontal cortex. Most of these genes were related to neuronal plasticity, protein phosphorylation, Са2+ homeostasis, hypoxia, immune processes, and apoptosis. Between the ages of 5 and 18 months, there were changes in the expression of 499 genes in Wistar rats and changes in the expression of 5500 genes in OXYS rats. Only 333 genes were common between these sets. This finding points to differences in the mechanisms and rates of age-related changes in the brain between normal aging and the period of development of AD-specific neurodegenerative processes.https://vavilov.elpub.ru/jour/article/view/434alzheimer’s diseaseoxys ratsbrain transcriptomerna-seq |
| spellingShingle | N. A. Stefanova E. E. Korbolina N. I. Ershov E. I. Rogaev N. G. Kolosova Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease development Вавиловский журнал генетики и селекции alzheimer’s disease oxys rats brain transcriptome rna-seq |
| title | Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease development |
| title_full | Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease development |
| title_fullStr | Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease development |
| title_full_unstemmed | Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease development |
| title_short | Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease development |
| title_sort | changes in the transcriptome of the prefrontal cortex of oxys rats as the signs of alzheimer s disease development |
| topic | alzheimer’s disease oxys rats brain transcriptome rna-seq |
| url | https://vavilov.elpub.ru/jour/article/view/434 |
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