Developmental patterns in the hippocampal transcriptome of the vervet monkey
Ontology highlight
ABSTRACT:
ORGANISM(S): Chlorocebus sabaeus
PROVIDER: GSE136255 | GEO | 2020/08/21
REPOSITORIES: GEO
Similar Datasets
Project description:Characterization of transcriptomic variation is emerging as a critical tool for understanding how quantitative trait loci (QTL) contribute to complex phenotypes. Human transcriptomic studies are limited by factors such as the feasibility of invasive tissue collection or variable environmental exposures that can be readily overcome in non-human primate (NHP) models. We characterized transcriptomic variation across multiple tissues and developmental stages and between individuals in 59 vervet monkeys from the Vervet Research Colony extended pedigree. We conducted RNA sequencing across early (7, 90 days, and one year) and later (1.25, 1.5, 1.75, 2, 2.5, 3, and 4+ years old) developmental time points in 6 individuals at each stage in five tissue types: two brain tissues from hippocampus and caudate, two endocrine tissues (pituitary and adrenal) and two peripheral tissues serving as a source of biomarkers (blood and fibroblasts)
2014-02-12 | E-MTAB-4404 | biostudies-arrayexpress
Project description:The hippocampus is part of a brain network essential for memory function. Paradoxically, the hippocampus is also the brain structure that is most sensitive to hypoxic-ischemic episodes. Here we show that the expression of genes associated with glycolysis and glutamate metabolism in astrocytes and the coverage of excitatory synapses by astrocytic processes undergo significant decreases in the CA1 field of the monkey hippocampus during postnatal development. Given the established role of astrocytes in the regulation of glutamate concentration in the synaptic cleft, our findings indicate that a developmental decrease in astrocytic processes underlies the selective vulnerability of CA1 during hypoxic-ischemic episodes in adulthood, its decreased susceptibility to febrile seizures with age, as well as contribute to the emergence of selective, adult-like memory function. Regulation of gene expression in the postnatally developing hippocampus might contribute to the emergence of selective memory function. However, the mechanisms that underlie the co-regulation of expression of hundreds of genes in different cell types at specific ages in distinct hippocampal regions have yet to be elucidated. By performing genome-wide microarray analyses of gene expression in distinct regions of the monkey hippocampal formation during early postnatal development, we identified one particular group of genes exhibiting a down-regulation of expression, between birth and six months of age in CA1 and after one year of age in CA3, to reach expression levels observed at 6-12 years of age. Bioinformatics analyses using NCBI, miRBase, TargetScan, microRNA.org and Affymetrix tools identified a number of miRNAs capable of regulating the expression of these genes simultaneously in different cell types, i.e., in neurons, astrocytes and oligodendrocytes. Interestingly, sixty-five percent of these miRNAs are conserved across species, from rodents to humans; whereas thirty-five percent are specific to primates, including humans. In addition, we found that some genes exhibiting greater down-regulation of their expression were the predicted targets of a greater number of these miRNAs. In sum, miRNAs may play a fundamental role in the co-regulation of gene expression in different cell types. This mechanism is partially conserved across species, and may thus contribute to the similarity of basic hippocampal characteristics across mammals. This mechanism also exhibits a phylogenetic diversity that may contribute to more subtle species differences in hippocampal structure and function observed at the cellular level. Sixteen male rhesus monkeys (Macaca mulatta; four 1-day-olds, four 6-month-olds, four 1-year-olds and four 6-12-year-olds) were used for this study. Monkeys were injected with an overdose of sodium pentobarbital (50 mg/kg i.v., Fatal-Plus, Vortech Pharmaceuticals, Dearborn, MI) and the brain rapidly extracted. Five-millimeter thick slices of the brain were cut and stored overnight in RNAlaterä (Ambion, Austin, TX) at 4oC. Brain slices were then frozen in liquid nitrogen and re-sectioned at 100 µm for microdissection. Five hippocampal regions were microdissected, including the entorhinal cortex (all layers at the mid-rostrocaudal level; intermediate division, Ei), and all layers of the dentate gyrus, CA3, CA1 and subiculum at mid-rostrocaudal level of the body of the hippocampus (at the level of the lateral geniculate nucleus). Only the mid-transverse portion of each region was dissected to ensure the specificity of the sample. RNA was isolated with Trizol® and single stranded cDNA synthesized starting with 10 µg of total RNA. The sample from each region from each monkey was run on a separate chip, thus totaling 4 (animals per age) X 4 (ages) X 5 (regions) = 80 independent chips.
2012-09-30 | E-GEOD-32590 | biostudies-arrayexpress
Project description:Age-related cognitive decline is a serious health concern in our aging society. Decreased cognitive function observed during healthy brain aging is most likely caused by changes in brain connectivity and synaptic dysfunction in particular brain regions. Here we show that aged C57BL/6J wildtype mice have hippocampus-dependent spatial memory impairments. To identify the molecular mechanisms that are relevant to these memory deficits we investigated the temporal profile of mouse hippocampal synaptic proteome changes at 20, 40, 50, 60, 70, 80, 90 and 100 weeks of age. Extracellular matrix proteins were the only group of proteins that showed a robust and progressive upregulation over time. This was confirmed by immunoblotting and histochemical analysis, indicating that the increased levels of hippocampal extracellular matrix may limit synaptic plasticity as a potential cause of age-related cognitive decline. In addition, we observed that stochasticity in synaptic protein expression increased with age, in particular for proteins that were previously linked with various neurodegenerative diseases, whereas low variance in expression was observed for proteins that play a basal role in neuronal function and synaptic neurotransmission. Together, our findings show that both specific changes and increased variance in synaptic protein expression are associated with aging and may underlie reduced synaptic plasticity and impaired cognitive performance at old age.
2014-09-10 | PXD001135 | Pride
Project description:Developmental patterns in the hippocampal transcriptome of the vervet monkey
| PRJNA561769 | ENA
Project description:The hippocampus is part of a brain network essential for memory function. Paradoxically, the hippocampus is also the brain structure that is most sensitive to hypoxic-ischemic episodes. Here we show that the expression of genes associated with glycolysis and glutamate metabolism in astrocytes and the coverage of excitatory synapses by astrocytic processes undergo significant decreases in the CA1 field of the monkey hippocampus during postnatal development. Given the established role of astrocytes in the regulation of glutamate concentration in the synaptic cleft, our findings indicate that a developmental decrease in astrocytic processes underlies the selective vulnerability of CA1 during hypoxic-ischemic episodes in adulthood, its decreased susceptibility to febrile seizures with age, as well as contribute to the emergence of selective, adult-like memory function. Regulation of gene expression in the postnatally developing hippocampus might contribute to the emergence of selective memory function. However, the mechanisms that underlie the co-regulation of expression of hundreds of genes in different cell types at specific ages in distinct hippocampal regions have yet to be elucidated. By performing genome-wide microarray analyses of gene expression in distinct regions of the monkey hippocampal formation during early postnatal development, we identified one particular group of genes exhibiting a down-regulation of expression, between birth and six months of age in CA1 and after one year of age in CA3, to reach expression levels observed at 6-12 years of age. Bioinformatics analyses using NCBI, miRBase, TargetScan, microRNA.org and Affymetrix tools identified a number of miRNAs capable of regulating the expression of these genes simultaneously in different cell types, i.e., in neurons, astrocytes and oligodendrocytes. Interestingly, sixty-five percent of these miRNAs are conserved across species, from rodents to humans; whereas thirty-five percent are specific to primates, including humans. In addition, we found that some genes exhibiting greater down-regulation of their expression were the predicted targets of a greater number of these miRNAs. In sum, miRNAs may play a fundamental role in the co-regulation of gene expression in different cell types. This mechanism is partially conserved across species, and may thus contribute to the similarity of basic hippocampal characteristics across mammals. This mechanism also exhibits a phylogenetic diversity that may contribute to more subtle species differences in hippocampal structure and function observed at the cellular level.
2012-09-30 | GSE32590 | GEO
Project description:In this study, we determined the effect of chronic consistent hypoxia (CCH) and chronic intermittent hypoxia (CIH) on global gene expression in cortical and hippocampal region of developing mouse brain using long-oligo beadschip arrays. Keywords: Gene expression profile Control-Cortex: Cortical samples from 16 days old mice were analysed on whole-genome expression chips to reveal expression profile at this developmental stage. Used as control for Chronic Hypoxia Treated cortical samples. CCH-Cortex: Cortical samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression profile following 2-week CCH treatment. CIH-Cortex: Cortical samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression profile following 2-week CIH treatment. Control-Hippocampus: Hippocampal samples from 16 days old mice were analysed on whole-genome expression chips to reveal expression profile at this developmental stage. Used as control for Chronic Hypoxia Treated hippocampal samples. CCH-Hippocampus: Hippocampal samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression following 2-week CCH treatment. CIH-Hippocampus: Hippocampal samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression following 2-week CIH treatment.
2010-06-25 | E-GEOD-8262 | biostudies-arrayexpress
Project description:Background: The risk for dementia increases exponentially from the seventh decade of life. Identifying and understanding the biochemical changes that sensitize the ageing brain to neurodegeneration will provide new opportunities for dementia prevention and treatment. This study aimed to determine how ageing and major genetic risk factors for dementia affect the hippocampal proteome and lipidome of neurologically-normal humans over the age of 65. The hippocampus was chosen as it is highly susceptible to atrophy with ageing and in several neurodegenerative diseases. Methods: Mass spectrometry-based proteomic and lipidomic analysis of CA1 hippocampus samples from 74 neurologically normal human donors, aged 66 – 104, was used in combination with multiple regression models and gene set enrichment analysis to identify age-dependent changes in the proteome and lipidome. ANOVA was used to test the effect of major dementia risk alleles in the TMEM106B and APOE genes on the hippocampal proteome and lipidome, adjusting for age, gender, and post-mortem interval. Fibrillar C-terminal TMEM106B fragments were isolated using sarkosyl fractionation and quantified by immunoblotting. Results: Forty proteins were associated with age at false discovery rate-corrected P<0.05, including proteins that regulate cell adhesion, the cytoskeleton, amino acid and lipid metabolism, and ribosomal subunits. TMEM106B, a regulator of lysosomal and oligodendrocyte function, was regulated with greatest effect size. The increase in TMEM106B levels with ageing was specific to carriers of the rs1990622-A allele in the TMEM106B gene that increases risk for frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, and hippocampal sclerosis with ageing. Rs1990622-A was also associated with higher TMEM106B fibril content. Hippocampal lipids were not significantly affected by APOE genotype, however levels of myelin-enriched sulfatides and hexosylceramides were significantly lower, and polyunsaturated phospholipids were higher, in rs1990622-A carriers after controlling for APOE genotype. Conclusions: Our study demonstrates that TMEM106B protein abundance is increased with brain ageing in humans, establishes that dementia risk allele rs1990622-A predisposes to TMEM106B fibril formation in the hippocampus, and provides the first evidence that rs1990622-A affects brain lipid homeostasis, particularly myelin lipids. Our data suggests that TMEM106B is one of a growing list of major dementia risk genes that affect glial lipid metabolism.
2023-09-21 | PXD043880 | Pride
Project description:The ability to assign expression patterns to individual cell types that constitute a tissue is a major challenge in RNA expression analysis. This especially applies to brain given the plethora of different cells coexisting in that tissue. Here, we derived cell-type specific transcriptome signatures from existing single cell RNA data and integrated these signatures with a newly generated dataset of expression (bulk RNA-seq) of the postnatal developing hippocampus. This integrated analysis allowed us to provide a comprehensive and unbiased prediction of the differentiation drivers for 10 different hippocampal cell types and describe how the different cell types interact to support crucial developmental stages. Our integrated analysis provides a reliable resource of predicted differentiation drivers and insight into the multifaceted aspects of the cells in hippocampus during development.
2018-01-30 | GSE79380 | GEO
Project description:This study identified the specific types of hippocampal neurons whose axons are vulnerable to amyloid-β accumulation. We used the inDropsTM platform to sequence 8 libraries: 5 libraries from the hippocampus of Alzheimer’s disease mice at 12,20, and, 24 weeks of age, and 3 libraries from the hippocampus of normal age-matched mice for the purpose of finding the selectively vulnerable hippocampal neuron type. 22,233 cells with 72,146 transcriptomes were collected after quality control was completed. When the 5,468 neurons that were marked by the expression of Snap25, Syt1, Ndrg4, and Meg3 were examined, we found that three types of neurons, such as somatostatin, chromogranin B, and calbindin-expressing neurons in the hippocampus, were selectively vulnerable to amyloid-β overexpression.
2023-09-13 | GSE230240 | GEO
Project description:We examined the genetic profile of postmortem brain (hippocampal) samples; 15 brains from patients diagnosed with MDD were matched to brains from healthy subjects based on gender, race and age. Gene expression profiles in the dentate gyrus and CA1 subregions of the hippocampus were assessed by cDNA hybridization to 48K human HEEBO whole genome microarrays (Microarray, Inc).
2010-10-17 | GSE24095 | GEO