title: Absence of IFNγ promotes hippocampal plasticity and enhances cognitive performance.
abstract: Cognitive functioning can be differentially modulated by components of the immune system. Interferon-γ (IFNγ) is a pro-inflammatory cytokine whose production is altered in many conditions displaying some degree of cognitive deficits, although its role in cognitive functioning is still unclear. Here we show that the absence of IFNγ selectively enhances cognitive behaviours in tasks in which the hippocampus is implicated. Moreover, the absence of IFNγ leads to volumetric and cell density changes that are restricted to the dorsal part of the hippocampus. In the dorsal hippocampus, the absence of this pro-inflammatory cytokine leads to an increase in the numbers of newly born neurons in the subgranular zone of the dentate gyrus (DG), an adult neurogenic niche known to support learning and memory, and to an enlargement of the dendritic arborization of DG granule and cornu ammonis (CA)1 pyramidal neurons. Moreover, it also modestly impacts synaptic plasticity, by decreasing the paired-pulse facilitation in the Schaffer collateral to CA1 pyramidal cell synapses. Taken together, our results provide evidence that IFNγ is a negative regulator of hippocampal functioning, as its absence positively impacts on dorsal hippocampus structure, cell density, neuronal morphology and synaptic plasticity. Importantly, these neuroplastic changes are associated with improved performance in learning and memory tasks. Therefore, blockage of the IFNγ signalling may present as promising therapeutic targets for the treatment of inflammation-associated cognitive dysfunction.
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|Life and Health Sciences Research Institute, 3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-3037-9635
authors.initials: S
authors.lastname: Monteiro
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|Life and Health Sciences Research Institute, 3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: F M
authors.initials: FM
authors.lastname: Ferreira
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|Life and Health Sciences Research Institute, 3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: V
authors.initials: V
authors.lastname: Pinto
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|Life and Health Sciences Research Institute, 3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-6512-996X
authors.initials: S
authors.lastname: Roque
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|Life and Health Sciences Research Institute, 3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Morais
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|Life and Health Sciences Research Institute, 3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: de Sá-Calçada
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|Life and Health Sciences Research Institute, 3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Mota
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|Life and Health Sciences Research Institute, 3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Correia-Neves
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|Life and Health Sciences Research Institute, 3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: J J
authors.initials: JJ
authors.lastname: Cerqueira
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007371:Interferon-gamma; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*
chemical_list: D007371:Interferon-gamma