Microglia‐Derived Vitamin D Binding Protein Mediates Synaptic Damage and Induces Depression by Binding to the Neuronal Receptor Megalin DOI Creative Commons
Yan Kong, Xian Zhang, Ling Li

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

Abstract Vitamin D binding protein (VDBP) is a potential biomarker of major depressive disorder (MDD). This study demonstrates for the first time that VDBP highly expressed in core emotion‐related brain regions mice susceptible to chronic unpredictable mild stress (CUMS). Specifically, overexpression microglia (MG)‐derived prelimbic leads depression‐like behavior and aggravates CUMS‐induced phenotypes mice, whereas conditional knockout MG‐derived can reverse both neuronal damage behaviors. Mechanistically, with receptor megalin mediates downstream SRC signaling pathway, leading synaptic These events may be caused by biased activation inhibitory neurons excitatory–inhibitory imbalance. Importantly, this has effectively identified as pivotal mediator interplay between via its interaction intricate impacts on functions, thus offering promising therapeutic target MDD.

Language: Английский

Astrocytic pleiotrophin deficiency in the prefrontal cortex contributes to stress-induced depressive-like responses in male mice DOI Creative Commons
Dongmei Chi, Kun Zhang, Jianxing Zhang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 14, 2025

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.

Language: Английский

Citations

0
S‐ketamine Alleviates Neuroinflammation and Attenuates Lipopolysaccharide‐Induced Depression Via Targeting SIRT2 DOI Creative Commons
Cong Lin, Xiaoxuan Zhou, Mingqi Li

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Depression, a pervasive mental health condition, has increasingly been linked to neuroinflammation, as evidenced by elevated levels of pro-inflammatory markers such TNF-α and IL-1β observed in patients, which underscores the role inflammation its pathophysiology. This study investigates differential effects S-ketamine (S-KET) R-ketamine (R-KET) on inflammation-induced depression using lipopolysaccharide (LPS)-induced mouse model. Results showed that S-KET, but not R-KET, significantly alleviated depressive-like behaviors reduced factors medial prefrontal cortex (mPFC). Activity-based protein profiling identified SIRT2 key intracellular target with direct binding at Q167 residue, whereas R-KET no binding. S-KET enhanced interaction NF-κB subunit p65, reducing acetylation suppressing gene expression, seen R-KET. In vitro studies RNA interference inhibitor AK-7, along vivo pharmacological blockade, confirmed is crucial for anti-inflammatory antidepressant actions S-KET. These findings suggest mediates therapeutic highlighting potential treating inflammation-associated depression. provides novel insights into stereospecific ketamine enantiomers promise targeting neuroinflammatory

Language: Английский

Citations

0
Astrocytes: a potential avenue for depression and cancer DOI Creative Commons
Chenglin Lu, Xiong Cao

Brain Behavior and Immunity Integrative, Journal Year: 2025, Volume and Issue: unknown, P. 100124 - 100124

Published: April 1, 2025

Language: Английский

Citations

0
Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications DOI Creative Commons

Kunying Zhao,

Yuxiao Zhang,

Shuda Yang

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 23, 2025

Major depressive disorder (MDD) is one of the most common mental health conditions, characterized by pervasive and persistent low mood, self-esteem, a loss interest or pleasure in activities that are typically enjoyable. Despite decades research into etiology pathophysiological mechanisms depression, therapeutic outcomes for many individuals remain less than expected. A promising new area focuses on stress-induced neuroinflammatory processes, such as excessive activation crosstalk microglia astrocytes central nervous system under stress, well elevated levels pro-inflammatory cytokines, which closely linked to onset progression depression. This review summarizes through neuroinflammation induces promotes development also highlights effective roles small molecules with anti-inflammatory activity treatment MDD. Understanding specific further impacts using technologies single-cell RNA sequencing elucidate subtypes interactions great importance developing more strategies

Language: Английский

Citations

0
Microglia‐Derived Vitamin D Binding Protein Mediates Synaptic Damage and Induces Depression by Binding to the Neuronal Receptor Megalin DOI Creative Commons
Yan Kong, Xian Zhang, Ling Li

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

Abstract Vitamin D binding protein (VDBP) is a potential biomarker of major depressive disorder (MDD). This study demonstrates for the first time that VDBP highly expressed in core emotion‐related brain regions mice susceptible to chronic unpredictable mild stress (CUMS). Specifically, overexpression microglia (MG)‐derived prelimbic leads depression‐like behavior and aggravates CUMS‐induced phenotypes mice, whereas conditional knockout MG‐derived can reverse both neuronal damage behaviors. Mechanistically, with receptor megalin mediates downstream SRC signaling pathway, leading synaptic These events may be caused by biased activation inhibitory neurons excitatory–inhibitory imbalance. Importantly, this has effectively identified as pivotal mediator interplay between via its interaction intricate impacts on functions, thus offering promising therapeutic target MDD.

Language: Английский

Citations

0