Acute Inflammation Alters Brain Energy Metabolism in Mice and Humans: Role in Suppressed Spontaneous Activity, Impaired Cognition, and Delirium.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
John KealyColm Cunningham

Abstract

Systemic infection triggers a spectrum of metabolic and behavioral changes, collectively termed sickness behavior, which while adaptive, can affect mood and cognition. In vulnerable individuals, acute illness can also produce profound, maladaptive, cognitive dysfunction including delirium, but our understanding of delirium pathophysiology remains limited. Here, we used bacterial lipopolysaccharide (LPS) in female C57BL/6J mice and acute hip fracture in humans to address whether disrupted energy metabolism contributes to inflammation-induced behavioral and cognitive changes. LPS (250 µg/kg) induced hypoglycemia, which was mimicked by interleukin (IL)-1β (25 µg/kg) but not prevented in IL-1RI-/- mice, nor by IL-1 receptor antagonist (IL-1RA; 10 mg/kg). LPS suppression of locomotor activity correlated with blood glucose concentrations, was mitigated by exogenous glucose (2 g/kg), and was exacerbated by 2-deoxyglucose (2-DG) glycolytic inhibition, despite preventing IL-1β synthesis. Using the ME7 model of chronic neurodegeneration in female mice, to examine vulnerability of the diseased brain to acute stressors, we showed that LPS (100 µg/kg) produced acute cognitive dysfunction, selectively in those animals. These acute cognitive ...Continue Reading

Citations

Dec 31, 2020·Brain, Behavior, and Immunity·Jennifer C Felger, Lucile Capuron
Nov 14, 2020·Nature Reviews. Disease Primers·Jo Ellen WilsonE Wesley Ely
Dec 15, 2020·Neuroscience and Biobehavioral Reviews·Felipe Figueredo SaviCristiane Ritter
May 1, 2021·Journal of Clinical Medicine·Yoshihisa FujinamiJoji Kotani
May 14, 2021·Neuropsychiatric Disease and Treatment·Anita Nitchingham, Gideon A Caplan
May 18, 2021·Frontiers in Aging Neuroscience·Giuseppe BellelliPaolo Mazzola
Jun 3, 2021·Pharmaceuticals·Carolina Araújo MoraesJoana Costa d'Avila
Jun 16, 2021·The Journal of Clinical Investigation·Marie HanscomTerez Shea-Donohue
Jul 6, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xinyi GuMingmei Zhou
Nov 10, 2021·Annual Review of Medicine·Niall T PrendergastTimothy D Girard

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Methods Mentioned

BETA
Enzyme linked immunoabsorbent assay
ELISA

Software Mentioned

SPSS
GraphPad Prism

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