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

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Abstract

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.

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Acknowledgments

We are grateful for the technical support of the Core Facilities, Zhejiang University School of Medicine. This work was supported by the National Natural Science Foundation of China (82001424 and 82171176), and the Key Program of the Natural Science Foundation of Zhejiang, China (LZ19H090003).

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  1. Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China

    Yeru Chen, Du Zheng, Hongwei Wang, Shuxia Zhang, Youfa Zhou, Xinlong Ke & Gang Chen

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  1. Yeru Chen
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  2. Du Zheng
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Correspondence to Gang Chen.

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Chen, Y., Zheng, D., Wang, H. et al. Lipocalin 2 in the Paraventricular Thalamic Nucleus Contributes to DSS-Induced Depressive-Like Behaviors. Neurosci. Bull. 39, 1263–1277 (2023). https://doi.org/10.1007/s12264-023-01047-4

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