title: Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation.
abstract: Psychological stress causes adaptive changes in the nervous system directed toward maintaining homoeostasis. These biochemical and structural mechanisms regulate animal behavior, and their malfunction may result in various forms of affective disorders. Here we found that the lipocalin-2 (Lcn2) gene, encoding a secreted protein of unknown neuronal function, was up-regulated in mouse hippocampus following psychological stress. Addition of lipocalin-2 to cultured hippocampal neurons reduced dendritic spine actin's mobility, caused retraction of mushroom spines, and inhibited spine maturation. These effects were further enhanced by inactivating iron-binding residues of Lcn-2, suggesting that they were facilitated by the iron-free form of Lcn-2. Concurrently, disruption of the Lcn2 gene in mice promoted stress-induced increase in spine density and caused an increase in the proportion of mushroom spines. The above changes correlated with higher excitability of CA1 principal neurons and with elevated stress-induced anxiety in Lcn-2(-/-) mice. Our study demonstrates that lipocalin-2 promotes stress-induced changes in spine morphology and function to regulate neuronal excitability and anxiety.
authors.affiliation: Department of Cell Physiology and Pharmacology,  University of Leicester, Leicester LE1 9HN,  United Kingdom.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Mucha
authors.forename: Anna E
authors.initials: AE
authors.lastname: Skrzypiec
authors.forename: Emanuele
authors.initials: E
authors.lastname: Schiavon
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Attwood
authors.forename: Eva
authors.initials: E
authors.lastname: Kucerova
authors.forename: Robert
authors.initials: R
authors.lastname: Pawlak
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D049229:Dendritic Spines / Q000502:physiology*; D007150:Immunohistochemistry; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000209:Acute-Phase Proteins; D017931:DNA Primers; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse