Lipocalin 2 in the Paraventricular Thalamic Nucleus Contributes to DSS-Induced Depressive-Like Behaviors

The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel diseases(IBD)than in the general population.The mechanisms underlying dextran sulfate sodium(DSS)-induced depressive-like behaviors are still unclear.We clarified that IBD mice induced by repeated administration of DSS presented depressive-like behaviors.The paraventricular thalamic nucleus(PVT)was regarded as the activated brain region by the number of c-fos-labeled neurons.RNA-sequencing analysis showed that lipocalin 2(Lcn2)was upregulated in the PVT of mice with DSS-induced depressive behaviors.Upregulating Lcn2 from neuronal activity induced dendritic spine loss and the secreted protein induced chemokine expression and subsequently contributed to microglial activation leading to blood-brain barrier permeability.Moreover,Lcn2 silencing in the PVT alleviated the DSS-induced depressive-like behaviors.The present study demonstrated that elevated Lcn2 in the PVT is a critical factor for DSS-induced depressive behaviors.