ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Aging-related gene expression in hippocampus proper compared with dentate gyrus is selectively associated with metabolic syndrome variables in rhesus monkeys.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
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- Brain Insulin Signaling, Alzheimer Disease Pathology, and Cognitive Function.Annals of neurology · 2020Article
- Candesartan Neuroprotection in Rat Primary Neurons Negatively Correlates with Aging and Senescence: a Transcriptomic Analysis.Molecular neurobiology · 2020Article
- Longevity: Lesson from Model Organisms.Genes · 2019Review
- White Matter is the Predilection Site of Late-Delayed Radiation-Induced Brain Injury in Non-Human Primates.Radiation research · 2019Article
- FK506-Binding Protein 12.6/1b, a Negative Regulator of [CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Sexually divergent induction of microglial-associated neuroinflammation with hippocampal aging.Journal of neuroinflammation · 2017Article
- Calcium's role as nuanced modulator of cellular physiology in the brain.Biochemical and biophysical research communications · 2017Review
- Hippocampal Transcriptomic Profiles: Subfield Vulnerability to Age and Cognitive Impairment.Frontiers in aging neuroscience · 2017Article
- Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.Neurotoxicity research · 2016Review
- Contributions of Nonhuman Primates to Research on Aging.Veterinary pathology · 2016Review
- Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.The journals of gerontology. Series A, Biological sciences and medical sciences · 2016Article
- White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.EBioMedicine · 2015Article
- The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity.Neurobiology of aging · 2015Article
- Electroacupuncture improves cognitive deficits associated with AMPK activation in SAMP8 mice.Metabolic brain disease · 2015Article
- Aging-related gene signature regulated by Nlrp3 predicts glioma progression.American journal of cancer research · 2015Article
- Integrative Transcriptome Profiling of Cognitive Aging and Its Preservation through Ser/Thr Protein Phosphatase Regulation.PloS one · 2015Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Age-dependent metabolic syndrome (MetS) is a well established risk factor for cardiovascular disease, but it also confers major risk for impaired cognition in normal aging or Alzheimer's disease (AD). However, little is known about the specific pathways mediating MetS-brain interactions. Here, we performed the first studies quantitatively linking MetS variables to aging changes in brain genome-wide expression and mitochondrial function. In six young adult and six aging female rhesus monkeys, we analyzed gene expression in two major hippocampal subdivisions critical for memory/cognitive function [hippocampus proper, or cornu ammonis (CA), and dentate gyrus (DG)]. Genes that changed with aging [aging-related genes (ARGs)] were identified in each region. Serum variables reflecting insulin resistance and dyslipidemia were used to construct a quantitative MetS index (MSI). This MSI increased with age and correlated negatively with hippocampal mitochondrial function (state III oxidation). More than 2000 ARGs were identified in CA and/or DG, in approximately equal numbers, but substantially more ARGs in CA than in DG were correlated selectively with the MSI. Pathways represented by MSI-correlated ARGs were determined from the Gene Ontology Database and literature. In particular, upregulated CA ARGs representing glucocorticoid receptor (GR), chromatin assembly/histone acetyltransferase, and inflammatory/immune pathways were closely associated with the MSI. These results suggest a novel model in which MetS is associated with upregulation of hippocampal GR-dependent transcription and epigenetic coactivators, contributing to decreased mitochondrial function and brain energetic dysregulation. In turn, these MSI-associated neuroenergetic changes may promote inflammation, neuronal vulnerability, and risk of cognitive impairment/AD.
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