Dataset Information

Distinct transcriptome expression of the temporal cortex of the primate Microcebus murinus during brain aging versus Alzheimer's disease-like pathology.

ABSTRACT: Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD). However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix). Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, "AD-like" animals that presented ß-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays), we identified 47 genes that discriminated young from healthy old and "AD-like" animals. These findings were confirmed by principal component analysis (PCA). ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA) with significant changes of expression in old and "AD-like" in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in "AD-like" animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the "AD-like" group. Functional categorization showed that most of the genes that were up-regulated in healthy old animals and down-regulated in "AD-like" animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in "AD-like" animals. These results open the way to new exploration of physiological and "AD-like" aging in primates.

SUBMITTER: Abdel Rassoul R

PROVIDER: S-EPMC2940844 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Distinct transcriptome expression of the temporal cortex of the primate Microcebus murinus during brain aging versus Alzheimer's disease-like pathology.

Abdel Rassoul Ronza R Alves Sabine S Pantesco Véronique V De Vos John J Michel Bernard B Perret Martine M Mestre-Francés Nadine N Verdier Jean-Michel JM Devau Gina G

PloS one 20100916 9

Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD). However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix). Gene expression profiles ...[more]

PMID: 20862281

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Project description:Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD). However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix). Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, "AD-like" animals that presented b-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays), we identified 47 genes that discriminated young from healthy old and "AD-like" animals. These findings were confirmed by principal component analysis (PCA). ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA) with significant changes of expression in old and "AD-like" in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in M-bM-^@M-^\AD-likeM-bM-^@M-^] animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the "AD-like" group. Functional categorization showed that most of the genes that were up-regulated in healthy old and down-regulated in "AD-like" animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in M-bM-^@M-^\AD-likeM-bM-^@M-^] animals. These results open the way to new exploration of physiological and M-bM-^@M-^\AD-likeM-bM-^@M-^] aging in primates. Microcebus murinus were divided in 3 groups: the first group included 6 young adults (4 females and 2 males), the second included 10 healthy old animals (7 females and 3 males) and the third one was composed by 2 "AD-like" old females. Since Microcebus murinus microarrays do not exist, we decided to use Affymetrix human genome chips (HG U133 plus 2), since studies have illustrated the feasibility of detecting non-human primate brain transcripts using human genome chips.

Project description:IntroductionThe gray mouse lemur (Microcebus murinus) is an important nonhuman primate model in biomedical research. Numerous studies investigated mouse lemur behavior and possible factors underlying interindividual variation in both, animal personality and cognitive performance. Some effects, such as an age-related decline in executive functioning, have robustly been found across laboratory colonies; however, little is known about the brain structural substrates in mouse lemurs.MethodsHere, we provide first exploratory data linking in vivo magnetic resonance imaging of 34 mouse lemurs to performance in a standardized, touchscreen-based task on object discrimination and reversal learning as well as to animal personality under different scenarios in an open field.ResultsHigh interindividual variability in both brain morphometric and behavioral measurements was found, but only few significant correlations between brain structure and behavior were revealed: Object discrimination learning was linked to the volume of the hippocampus and to temporal lobe thickness, while reversal learning was linked to thalamic volume and the thickness of the anterior cingulate lobe. Emergence latency into the open field correlated with volume of the amygdala. General exploration-avoidance in the empty open-field arena correlated with thicknesses of the anterior cingulate lobe and fronto-parietal substructures. Neophilia, assessed as exploration of a novel object placed in the arena, among others, related to the volume of the caudate nucleus.ConclusionIn summary, our data suggest a prominent role of temporal structures (including the hippocampus) for learning capability, as well as thalamic and anterior cingulate structures for cognitive flexibility and response inhibition. The amygdala, the anterior cingulate lobe, and the caudate nucleus are particularly linked to animal personality in the open-field setting. These findings are congruent with the comparative psychological literature and provide a valuable basis for future studies elucidating aspects of behavioral variation in this nonhuman primate model.

Project description:Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD). However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix). Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, "AD-like" animals that presented b-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays), we identified 47 genes that discriminated young from healthy old and "AD-like" animals. These findings were confirmed by principal component analysis (PCA). ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA) with significant changes of expression in old and "AD-like" in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in “AD-like” animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the "AD-like" group. Functional categorization showed that most of the genes that were up-regulated in healthy old and down-regulated in "AD-like" animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in “AD-like” animals. These results open the way to new exploration of physiological and “AD-like” aging in primates.

Dataset Information

Distinct transcriptome expression of the temporal cortex of the primate Microcebus murinus during brain aging versus Alzheimer's disease-like pathology.

Publications

Distinct transcriptome expression of the temporal cortex of the primate Microcebus murinus during brain aging versus Alzheimer's disease-like pathology.

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