AUTHOR=Ferreira Ana C., Pinto Vitor , Mesquita Sandro D., Novais Ashley , Sousa Joao C., Correia-Neves Margarida , Sousa Nuno , Palha Joana A., Marques Fernanda TITLE=Lipocalin-2 is involved in emotional behaviors and cognitive function JOURNAL=Frontiers in Cellular Neuroscience VOLUME=Volume 7 - 2013 YEAR=2013 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2013.00122 DOI=10.3389/fncel.2013.00122 ISSN=1662-5102 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.