Age and Sex Influence the Hippocampal Response and Recovery Following Sepsis.

Abstract:

: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.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Barter J,Kumar A,Stortz JA,Hollen M,Nacionales D,Efron PA,Moldawer LL,Foster TC

doi

10.1007/s12035-019-01681-y

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

8557-8572

issue

12

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-019-01681-y

journal_volume

56

pub_type

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