title: Stress-induced lipocalin-2 controls dendritic spine formation and neuronal activity in the amygdala.
abstract: Behavioural adaptation to psychological stress is dependent on neuronal plasticity and dysfunction at this cellular level may underlie the pathogenesis of affective disorders such as depression and post-traumatic stress disorder. Taking advantage of genome-wide microarray assay, we performed detailed studies of stress-affected transcripts in the amygdala - an area which forms part of the innate fear circuit in mammals. Having previously demonstrated the role of lipocalin-2 (Lcn-2) in promoting stress-induced changes in dendritic spine morphology/function and neuronal excitability in the mouse hippocampus, we show here that the Lcn-2 gene is one of the most highly upregulated transcripts detected by microarray analysis in the amygdala after acute restraint-induced psychological stress. This is associated with increased Lcn-2 protein synthesis, which is found on immunohistochemistry to be predominantly localised to neurons. Stress-naïve Lcn-2(-/-) mice show a higher spine density in the basolateral amygdala and a 2-fold higher rate of neuronal firing rate compared to wild-type mice. Unlike their wild-type counterparts, Lcn-2(-/-) mice did not show an increase in dendritic spine density in response to stress but did show a distinct pattern of spine morphology. Thus, amygdala-specific neuronal responses to Lcn-2 may represent a mechanism for behavioural adaptation to psychological stress.
authors.affiliation: University of Exeter Medical School, Exeter, United Kingdom.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Skrzypiec
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Shah
authors.forename: Emanuele
authors.initials: E
authors.lastname: Schiavon
authors.forename: Eva
authors.initials: E
authors.lastname: Baker
authors.forename: Nathan
authors.initials: N
authors.lastname: Skene
authors.forename: Robert
authors.initials: R
authors.lastname: Pawlak
authors.forename: Mariusz
authors.initials: M
authors.lastname: Mucha
mesh_terms: D000200:Action Potentials / Q000235:genetics; D017398:Alternative Splicing; D000679:Amygdala / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D016000:Cluster Analysis; D049229:Dendritic Spines; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D013315:Stress, Psychological / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D054834:Lipocalins