title: IFN-γ differentially modulates memory-related processes under basal and chronic stressor conditions.
abstract: Cytokines are inflammatory messengers that orchestrate the brain's response to immunological challenges, as well as possibly even toxic and psychological insults. We previously reported that genetic ablation of the pro-inflammatory cytokine, interferon-gamma (IFN-γ), attenuated some of the corticosteroid, cytokine, and limbic dopaminergic variations induced by 6 weeks of exposure to an unpredictable psychologically relevant stressor. Presently, we sought to determine whether a lack of IFN-γ would likewise modify the impact of chronic stress on hippocampus-dependent memory function and related neurotransmitter and neurotrophin signaling systems. As predicted, chronic stress impaired spatial recognition memory (Y-maze task) in the wild-type animals. In contrast, though the IFN-γ knockouts (KOs) showed memory disturbances in the basal state, under conditions of chronic stress these mice actually exhibited facilitated memory performance. Paralleling these findings, while overall the KOs displayed altered noradrenergic and/or serotonergic activity in the hippocampus and locus coeruleus, norepinephrine utilization in both of these memory-related brain regions was selectively increased among the chronically stressed KOs. However, contrary to our expectations, neither IFN-γ deletion nor chronic stressor exposure significantly affected nucleus accumbens dopaminergic neurotransmission or hippocampal brain-derived neurotrophic factor protein expression. These findings add to a growing body of evidence implicating cytokines in the often differential regulation of neurobehavioral processes in health and disease. Whereas in the basal state IFN-γ appears to be involved in sustaining memory function and the activity of related brain monoamine systems, in the face of ongoing psychologically relevant stress the cytokine may, in fact, act to restrict potentially adaptive central noradrenergic and spatial memory responses.
authors.affiliation: Department of Neuroscience, Carleton University Ottawa, ON, Canada.
authors.forename: Darcy
authors.initials: D
authors.lastname: Litteljohn
authors.affiliation: Faculty of Medicine, University of Toronto Toronto, ON, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Nelson
authors.affiliation: Department of Neuroscience, Carleton University Ottawa, ON, Canada.
authors.forename: Shawn
authors.initials: S
authors.lastname: Hayley
keywords: BDNF; cytokine; depression; hippocampus; knockout mouse; memory; monoamine