{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:23:27Z","timestamp":1787675007434,"version":"build-2784847793"},"reference-count":67,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroimmunomodulation"],"abstract":"<jats:p>Introduction: Depression is a common mental disease. Carboxypeptidase E (CPE) may be a therapeutic target for depression. This study aimed to investigate whether CPE regulates NOD-like receptor protein 3 (NLRP3) inflammasome signaling and affects pyroptosis, thereby improving cellular damage and depression-like behaviors in depressed mice. Methods: A mouse model of depression-like behavior was established with chronic unpredictable mild stress (CUMS) and treated with Lv-oe-CPE, an NLRP3 inflammasome activator (nigericin), or an NLRP3 inflammasome inhibitor (MCC950). Anxiety- and depression-like behaviors were assessed through open field test, forced swim test, tail suspension test, and sucrose preference test. Cellular damage in the hippocampal CA1 region was evaluated with H&amp;E and Nissl staining. CPE, gasdermin D-N (GSDMD-N), NLRP3, cleaved caspase 1, apoptosis-associated spot-like protein (ASC), oxidative stress, interleukin (IL)-1\u03b2, and IL-18 levels, and GSDMD-N-positive cells were assessed with Western blot, kits, and immunohistochemistry. Results: CPE was downregulated in the hippocampal CA1 region of CUMS mice, and its reexpression attenuate depression-like behaviors. CPE overexpression suppressed NLRP3, cleaved caspase 1, ASC, IL-1\u03b2, and IL-18 levels in the hippocampal CA1 region. NLRP3 inflammasome inactivation alleviated CA1 cellular damage to inhibit depressive-like behaviors, whereas its activation reversed the improving effect of CPE. CPE inactivated NLRP3 inflammasomes, thereby attenuating cell pyroptosis in the hippocampal CA1 region. Conclusions: CPE is downregulated in the hippocampal CA1 region of the mouse model of depression-like behavior. CPE overexpression can inhibit NLRP3 inflammasome activation and then reduce pyroptosis, hence repairing cellular damage in the hippocampal CA1 region and eventually suppressing depressive-like behaviors.<\/jats:p>","DOI":"10.1159\/000553608","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T16:01:18Z","timestamp":1784217678000},"page":"315-335","source":"Crossref","is-referenced-by-count":0,"title":["The Mechanism of Carboxypeptidase E Regulating NLRP3 Inflammasome Signaling in the Pathogenesis of Depression-Like Behaviors in 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