Lipocalin-2 is involved in emotional behaviors and cognitive function

Ana Catarina Ferreira, Vítor Pinto, Sandro Dá Mesquita, Ashley Novais, João C. Sousa, Margarida Correia-Neves, Nuno Sousa, Joana A. Palha, Fernanda Marques

Research output: Contribution to journalArticlepeer-review


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 stress54 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 (HPA) 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.

Original languageEnglish (US)
JournalFrontiers in Cellular Neuroscience
Issue numberJUL
StatePublished - Jul 11 2013


  • Anxiety
  • Behavior
  • Depression
  • Hippocampus
  • Lipocalin-2

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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