Downregulation of p120 catenin in the mouse hippocampus contributes to the development of depression-like phenotypes.

backgroundMajor depressive disorder (MDD) is a highly prevalent psychiatric disorder and one of the leading causes of disability worldwide. Neuroinflammation is strongly implicated in the pathophysiology of MDD, suggesting that regulators of neuroinflammatory signaling are feasible therapeutic targets. The CTNND1 gene encodes a member of the armadillo protein family termed p120 (or catenin delta) that functions in cell-cell adhesion and signal transduction, including among immune cells, suggesting immunomodulatory activity.

resultsWe report that systemic injection of the bacterial toxin lipopolysaccharide (LPS) induced depression-like behaviors in mice while concomitantly activating the neuroinflammatory NF-κB signaling pathway, upregulating interleukin (IL)-1β expression, and reducing p120 expression in the hippocampus. Moreover, shRNA-mediated knockdown of hippocampal p120 expression also activated the NF-κB signaling pathway, enhanced IL-1β expression, and induced the same depression-like behaviors. Similarly, both LPS treatment and p120 knockdown upregulated pNF-κB and IL-1β levels in pheochromocytoma-12 cells.

conclusionsThese findings suggest that p120 may function to prevent the development or expression of depressive symptoms by suppressing proinflammatory NF-κB-IL-1β signaling in the hippocampus. Targeting p120 may be a feasible therapeutic strategy to treat MDD.