Astrocytic pleiotrophin deficiency in the prefrontal cortex contributes to stress-induced depressive-like responses in male mice

• DOI: 10.1038/s41467-025-57924-1
• Publication Date: 2025-03-14T05:16:50Z
• Authors: Dongmei Chi; Kun Zhang; Jianxing Zhang; Zhaoli He; Hongxia Zhou; Wan Huang; Yang Liu; Jingxiu Huang; Weian Zeng; Xiaohui Bai; Chaopeng Ou; Handong Ouyang
• Keywords: Pleiotrophin

Astrocytes are closely linked to depression, and the prefrontal cortex (PFC) is an important brain region involved in major depressive disorder (MDD). However, underlying mechanism by which astrocytes within PFC contribute MDD remains unclear. Using single-nucleus RNA sequencing analyses, we show a significant reduction attenuated pleiotrophin-protein tyrosine phosphatase receptor type Z1 (PTN-PTPRZ1) signaling astrocyte-to-excitatory neuron communication of male patients. We find reduced PTN dorsomedial mice with depression induced chronic restraint social defeat stress. Knockdown astrocytic induces depression-related responses, reversed exogenous supplementation or overexpression PTN. The antidepressant effects exerted require interaction PTPRZ1 excitatory neurons, PTN-PTPRZ1 activates AKT pathway regulate responses. Our findings indicate PTN-PTPRZ1-AKT may be potential therapeutic target for MDD. but mechanisms remain Here, authors that pleiotrophin contributes depression-like phenotype mice.