Old Human Serum Increases Apoptosis and Molecular Ageing Markers In Human Hippocampal Progenitor Cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE106403 | GEO | 2017/11/02
SECONDARY ACCESSION(S): PRJNA416774
REPOSITORIES: GEO
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Project description:Old Human Serum Increases Apoptosis and Molecular Ageing Markers In Human Hippocampal Progenitor Cells
| PRJNA416774 | ENA
Project description:Age-related alteration in neural stem cell function is linked to neurodegenerative conditions and cognitive decline. In rodents, this can be reversed by exposure to a young systemic milieu and conversely, the old milieu can inhibit stem cell function in young rodents. In this study, we investigated the in vitro effect of the human systemic milieu on human hippocampal progenitor cells (HPCs) using human serum from early adulthood, mid-life and older age. We showed that neuroblast number following serum treatment is predictive of larger dentate gyrus, CA3, CA4 and whole hippocampus volumes and that allogeneic human serum from asymptomatic older individuals induced a two-fold increase in apoptotic cell death of HPCs compared with serum from young adults. General linear models revealed that variability in markers of proliferation and differentiation was partly attributable to use of antihypertensive medication and very mild cognitive decline among older subjects. Finally, using an endophenotype approach and whole-genome expression arrays, we showed upregulation of established and novel ageing molecular hallmarks in response to old serum. Serum from older subjects induced a wide range of cellular and molecular phenotypes, likely reflecting a lifetime of environmental exposures. Our findings support a role for the systemic enviroment in neural stem cell maintenance and are in line with others highlighting a distinction between neurobiological and chronological ageing. Finally, the herein described serum assay can be used by future studies to further analyse the effect of environmental exposures as well as to determine the role of the systemic environment in health and disease.
| S-EPMC8612606 | biostudies-literature
Project description:Hippocampal apoptosis is a characteristic feature of penumococcal meningitis associated with learning and memory deficitis as a sequel of the disease. We investigated the effect of vitamin B6 using an established infant rat model of experimental pneumococcal meningitis by histomorphology, transcriptomics and measurement of cellular nicotine amide adenine dinucleotide content. The data provides evidence that vitamin B6 is neuroprotecitve in terms of reduced hippocampal apoptosis involving reduction of the inflammatory response, preservation of cellular energy stores and up-regulated brain-derived neurotrophic factor levels.
2012-02-20 | E-MEXP-3555 | biostudies-arrayexpress
Project description: Not available
| S-EPMC3073456 | biostudies-literature
Project description:The cell fate transition from radial glial-like (RGL) cells to neurons and astrocytes is crucial for development and pathological conditions. Two chromatin repressors- the enhancer of zeste homolog 2 and suppressor of variegation 4-20 homolog, are highly associated with RGL cells in the hippocampus, implicating hippocampal cell fate commitment underlying these epigenetic regulations. Using a double knock-out mouse model, we demonstrated that loss of both chromatin repressors in the RGL population leads to deficits in hippocampal development. At the molecular level, single nuclei RNA-Seq revealed differential gene expression and provided mechanistic insight that dual chromatin repressors are critical for the maintenance of cycling cells in the dentate gyrus as well as the balance of cell trajectories between neuronal and astroglial lineages.
2022-02-01 | GSE185666 | GEO
Project description:BackgroundIn humans, interferon-α treatment for chronic viral hepatitis is a well-recognized clinical model for inflammation-induced depression, but the molecular mechanisms underlying these effects are not clear. Following peripheral administration in rodents, interferon-α induces signal transducer and activator of transcription-1 (STAT1) within the hippocampus and disrupts hippocampal neurogenesis.MethodsWe used the human hippocampal progenitor cell line HPC0A07/03C to evaluate the effects of 2 concentrations of interferon-α, similar to those observed in human serum during its therapeutic use (500 pg/mL and 5000 pg/mL), on neurogenesis and apoptosis.ResultsBoth concentrations of interferon-α decreased hippocampal neurogenesis, with the high concentration also increasing apoptosis. Moreover, interferon-α increased the expression of interferon-stimulated gene 15 (ISG15), ubiquitin-specific peptidase 18 (USP18), and interleukin-6 (IL-6) via activation of STAT1. Like interferon-α, co-treatment with a combination of ISG15, USP18, and IL-6 was able to reduce neurogenesis and enhance apoptosis via further downstream activation of STAT1. Further experiments showed that ISG15 and USP18 mediated the interferon-α-induced reduction in neurogenesis (potentially through upregulation of the ISGylation-related proteins UBA7, UBE2L6, and HERC5), while IL-6 mediated the interferon-α-induced increase in apoptosis (potentially through downregulation of aquaporin 4). Using transcriptomic analyses, we showed that interferon-α regulated pathways involved in oxidative stress and immune response (e.g., Nuclear Factor (erythroid-derived 2)-like 2 [Nrf2] and interferon regulatory factor [IRF] signaling pathway), neuronal formation (e.g., CAMP response element-binding protein [CREB] signaling), and cell death regulation (e.g., tumor protein(p)53 signaling).ConclusionsWe identify novel molecular mechanisms mediating the effects of interferon-α on the human hippocampus potentially involved in inflammation-induced neuropsychiatric symptoms.
| S-EPMC5793815 | biostudies-literature
Project description:Lithium is a first-line treatment for bipolar disorder, where it acts as a mood-stabilizing agent. Although its precise mechanism remains unclear, neuroimaging studies have shown that lithium accumulates in the hippocampus and that chronic use amongst bipolar disorder patients is associated with larger hippocampal volumes. Here, we tested the chronic effects of low (0.75 mM) and high (2.25 mM) doses of lithium on human hippocampal progenitor cells and used immunocytochemistry to investigate the effects of lithium on cell parameters implicated in neurogenesis. Corresponding RNA-sequencing and gene-set enrichment analyses were used to evaluate whether genes affected by lithium in our model overlap with those regulating the volume of specific layers of the dentate gyrus. We observed that high-dose lithium treatment in human hippocampal progenitors increased the generation of neuroblasts (P ≤ 0.01), neurons (P ≤ 0.01), and glia (P ≤ 0.001), alongside the expression of genes which regulate the volume of the molecular layer of the dentate gyrus. This study provides empirical support that adult hippocampal neurogenesis and gliogenesis are mechanisms that could contribute to the effects of lithium on human hippocampal volume.
2021-09-30 | GSE184930 | GEO
Project description:Lithium treatment and human hippocampal neurogenesis
| PRJNA767056 | ENA
Project description:In the present work, we gain insight into the impact of oligodendrocyte secreted factors on hippocampal GABAergic neuron physiology, and performed patch-clamp recordings followed by single-cell RNA sequencing of neurons. Our results demonstrate that the GABAergic neuron excitability is influenced by glial cells and oligodendrocyte-secreted factors. Moreover, we show specific ion channels alterations and find a correlation with electrophysiological parameters suggesting possible mechanisms for the OCM-induced regulation of neuronal function.
2023-02-22 | GSE146291 | GEO
Project description:To quantify associations between inflammatory biomarkers and hippocampal volume (HV) and to examine effect modification according to sex, race, and age.Cross-sectional analyses using generalized estimating equations to account for familial clustering; standardized ?-coefficients adjusted for age, sex, race, and education.Community cohorts in Jackson, Mississippi and Rochester, Minnesota.The Genetic Epidemiology Network of Arteriopathy study.C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors 1 (sTNFR-1) and 2 (sTNFR-2) from peripheral blood were measured in a sample of 773 non-Hispanic whites (61% women, aged 60.2 ± 9.8) and 514 African Americans (70% women, aged 63.9 ± 8.1) who also underwent brain magnetic resonance imaging. Biomarkers were standardized and compared according to sex, race and age with HV.In the full sample, higher sTNFR-1 and sTNFR-2 were associated with smaller HV. Each standard deviation (SD) increase in sTNFR-1 was associated with 59.1 mm(3) (95% confidence interval (CI) = -101.4 to -16.7 mm(3) ) smaller HV and each SD increase in sTNFR-2 associated with 48.8 mm(3) (95% CI = -92.2 to -5.3 mm(3) ) smaller HV. Relationships were stronger for sTNFR-2 in men (HV = -116.6 mm(3) for each SD increase, 95% CI = -201.0 to -32.1) than women (HV = -26.0 per SD increase, 95% CI = -72.4-20.5) and sTNFR-1 in non-Hispanic whites (HV = -84.7 mm(3) per SD increase, 95% CI = -142.2 to -27.1) than African Americans (HV = -14.1 mm(3) per SD increase, 95% CI = -78.3-50.1). Associations between IL-6 or CRP and HV were not supported.Higher levels of sTNFRs were associated cross-sectionally with smaller hippocampi. Longitudinal data are needed to determine whether these biomarkers may help to identify risk of late-life cognitive impairment.
| S-EPMC5026883 | biostudies-other