Age and Sex Influence the Hippocampal Response and Recovery Following Sepsis
Autor: | Dina C. Nacionales, McKenzie K. Hollen, Lyle L. Moldawer, Julie A. Stortz, Thomas C. Foster, Philip A. Efron, Jolie Barter, Ashok V. Kumar |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Aging Neurology Neuroscience (miscellaneous) Hippocampus Physiology Hippocampal formation Article Transcriptome Sepsis 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Immune system Medicine Animals Sex Characteristics business.industry Mortality rate Gene Expression Profiling Neurogenesis Cecal ligation and puncture medicine.disease Mice Inbred C57BL 030104 developmental biology Gene Ontology Gene Expression Regulation Cytokines Female business 030217 neurology & neurosurgery |
Zdroj: | Molecular Neurobiology |
ISSN: | 1559-1182 |
Popis: | Although in-hospital mortality rates for sepsis have decreased, survivors often experience lasting physical and cognitive deficits. Moreover, older adults are more vulnerable to long-term complications associated with sepsis. We employed a murine model to examine the influence of age and sex on the brain’s response and recovery following sepsis. Young (~ 4 months) and old (~ 20 months) mice (C57BL/6) of both sexes underwent cecal ligation and puncture (CLP) with restraint stress. The hippocampal transcriptome was examined in age- and sex-matched controls at 1 and 4 days post-CLP. In general, immune- and stress-related genes increased, while neuronal, synaptic, and glial genes decreased 1 day after CLP-induced sepsis. However, specific age and sex differences were observed for the initial responsiveness to sepsis as well as the rate of recovery examined on day 4. Young females exhibited a muted transcriptional response relative to young males and old females. Old females exhibited a robust shift in gene transcription on day 1, and while most genes recovered, genes linked to neurogenesis and myelination continued to be downregulated by day 4. In contrast, old males exhibited a more delayed or prolonged response to sepsis, such that neuronal and synaptic genes continued to decrease while immune response genes continued to increase on day 4. These results suggest that aging is associated with delayed recovery from sepsis, which is particularly evident in males. Electronic supplementary material The online version of this article (10.1007/s12035-019-01681-y) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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