TY - JOUR
T1 - Lipocalin-2 is involved in emotional behaviors and cognitive function
AU - Ferreira, Ana Catarina
AU - Pinto, Vítor
AU - Dá Mesquita, Sandro
AU - Novais, Ashley
AU - Sousa, João C.
AU - Correia-Neves, Margarida
AU - Sousa, Nuno
AU - Palha, Joana A.
AU - Marques, Fernanda
PY - 2013/7/11
Y1 - 2013/7/11
N2 - 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.
AB - 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.
KW - Anxiety
KW - Behavior
KW - Depression
KW - Hippocampus
KW - Lipocalin-2
UR - http://www.scopus.com/inward/record.url?scp=85081784246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081784246&partnerID=8YFLogxK
U2 - 10.3389/fncel.2013.00122
DO - 10.3389/fncel.2013.00122
M3 - Article
AN - SCOPUS:85081784246
SN - 1662-5102
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
IS - JUL
ER -