title: Lipocalin-2 is involved in emotional behaviors and cognitive function.
abstract: Lipocalin-2 (LCN2), an iron-related protein well described to participate in the innate immune response, has been shown to modulate spine morphology and to regulate neuronal excitability. In accordance, LCN2-null mice are reported to have stress-induced anxiety. Here we show that, under standard housing conditions, LCN2-null mice display anxious and depressive-like behaviors, as well as cognitive impairment in spatial learning tasks. These behavioral alterations were associated with a hyperactivation of the hypothalamic-pituitary-adrenal axis and with an altered brain cytoarchitecture in the hippocampus. More specifically, we found that the granular and pyramidal neurons of the ventral hippocampus, a region described to be associated with emotion, were hypertrophic, while neurons from the dorsal hippocampus, a region implicated in memory and cognition, were atrophic. In addition, LCN2-null mice presented synaptic impairment in hippocampal long-term potentiation. Whether the LCN2 effects are mediated through modulation of the level of corticosteroids or through a novel mechanism, the present observations bring further into light this immune-related protein as a player in the fine-tuning of behavior and of synaptic activity.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho Braga, Portugal ; ICVS/3B's - PT Government Associate Laboratory Braga/Guimarães, Portugal.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Ferreira
authors.forename: Vítor
authors.initials: V
authors.lastname: Pinto
authors.forename: Sandro
authors.initials: S
authors.lastname: Dá Mesquita
authors.forename: Ashley
authors.initials: A
authors.lastname: Novais
authors.forename: João C
authors.initials: JC
authors.lastname: Sousa
authors.forename: Margarida
authors.initials: M
authors.lastname: Correia-Neves
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.forename: Joana A
authors.initials: JA
authors.lastname: Palha
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
keywords: anxiety; behavior; depression; hippocampus; lipocalin-2
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