Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system
Neuropsychopharmacol. 2007-12-12; 33(10): 2341-2351
DOI: 10.1038/sj.npp.1301649
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1. Neuropsychopharmacology. 2008 Sep;33(10):2341-51. Epub 2007 Dec 12.
Aging exacerbates depressive-like behavior in mice in response to activation of
the peripheral innate immune system.
Godbout JP(1), Moreau M, Lestage J, Chen J, Sparkman NL, O’Connor J, Castanon N,
Kelley KW, Dantzer R, Johnson RW.
Author information:
(1)Department of Molecular Virology, Immunology and Medical Genetics, Institute
for Behavioral Medicine, The Ohio State University, Columbus, OH, USA.
Exposure to peripheral infections may be permissive to cognitive and behavioral
complications in the elderly. We have reported that peripheral stimulation of the
innate immune system with lipopolysaccharide (LPS) causes an exaggerated
neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice.
Because LPS also causes depressive behavior, the purpose of this study was to
determine whether aging is associated with an exacerbated depressive-like
response. We confirmed that LPS (0.33 mg/kg intraperitoneal) induced a protracted
sickness response in aged mice with reductions in locomotor and feeding
activities 24 and 48 h postinjection, when young adults had fully recovered. When
submitted to the forced swim test 24 h post-LPS, both young adult and aged mice
exhibited an increased duration of immobility. However, when submitted to either
the forced swim test or the tail suspension test 72 h post-LPS, an increased
duration of immobility was evident only in aged mice. This prolonged
depressive-like behavior in aged LPS-treated mice was associated with a more
pronounced induction of peripheral and brain indoleamine 2,3-dioxygenase and a
markedly higher turnover rate of brain serotonin (as measured by the ratio of
5-hydroxy-indoleacetic acid over 5-hydroxy-tryptamine) compared to young adult
mice at 24 post-LPS injection. These results provide the first evidence that
age-associated reactivity of the brain cytokine system could play a
pathophysiological role in the increased prevalence of depression observed in the
elderly.
DOI: 10.1038/sj.npp.1301649
PMCID: PMC2907915
PMID: 18075491 [Indexed for MEDLINE]