Introduction: Neuroinflammation plays an important role in the development of major depressive disorder (MDD). Osteopontin (OPN) is one of the key molecules involved in neuroinflammation. We demonstrate here for the first time a key role of OPN in lipopolysaccharide (LPS)-induced depressive-like behavioral syndrome.
Methods: Systemic administration of LPS (5 mg/kg) mimics distinct depressive-like behavior, which could significantly upregulate OPN expression in microglia/macrophage in the hippocampus. The neurobehavioral assessments, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), Western blot, immunofluorescent staining, flow cytometry cell staining and Golgi staining were performed.
Results: Similar to fluoxetine treatment (the positive control), OPN knockdown with shRNA lentivirus markedly reversed LPS-induced depressive-like behavior. Moreover, knockdown of OPN suppressed LPS-induced proinflammatory cytokine expression, microglial activation, dendritic spines loss, as well as unregulated PSD-95 and BDNF in the hippocampus.
Conclusion: We demonstrated that targeting OPN expression in microglia/macrophage might help to rescue LPS-induced depressive-like behavior. The underlying mechanism may relate to the modulation of neuroinflammation, BDNF signaling and synaptic structural complexity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jad.2023.02.105 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Metformin attenuated depressive-like behaviors by suppressing TRPV1/NLRP3 mediated neuroinflammation in the hypothalamus of allergic rhinitis mice.
Neuroscience
January 2025
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Department of Rhinology and Allergy, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Province Key Laboratory of Allergy and Immunology, Wuhan, China. Electronic address:
Background: In addition to nasal symptoms, allergic rhinitis (AR) has increasingly been reported to be associated with depression-like behaviors. Recent evidence suggests that neuroinflammation in the hypothalamus may cause these depressive symptoms in AR. However, the precise mechanisms and effective treatments remain to be elucidated.
View Article and Find Full Text PDFEsketamine alleviates LPS-induced depression-like behavior by activating Nrf2-mediated anti-inflammatory response in adolescent mice.
Neuroscience
January 2025
Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address:
Background: The mechanisms underlying esketamine's therapeutic effects remain elusive. The study aimed to explore the impact of single esketamine treatment on LPS-induced adolescent depressive-like behaviors and the role of Nrf2 regulated neuroinflammatory response in esketamine-produced rapid antidepressant efficacy.
Methods: Adolescent male C57BL/6J mice were randomly assigned to three groups: control, LPS, and LPS + esketamine (15 mg/kg, i.
Pentraxin 3 promotes microglial M2 polarization and excitatory synapse formation in the hippocampus in depression.
Int Immunopharmacol
January 2025
Department of Radiology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212001, China. Electronic address:
Depression is a prevalent mental illness that significantly impairs individuals' overall quality of life and physical well-being. However, the pathological mechanisms of depression remain unclear, and effective treatment strategies are urgently needed. Pentraxin 3 (PTX3), a long pentraxin protein, plays a significant role in various pathological conditions, including infections, immune responses, and tissue repair.
View Article and Find Full Text PDFSex-Differences Influence Depressive-Like Behaviour via Alterations in Microglial Expression of GIF-1, TREM2, and IL-1β in an Acute Lipopolysaccharide-Induced Murine Neuroinflammation Model.
Immunol Invest
December 2024
Doping Research Chair, Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia.
Background: Neurodegenerative diseases (NDs) have caused serious health issues worldwide. A growing body of evidence suggests a correlation between neuroinflammation and abnormal microglial activity with ND symptoms. Microglia survey play crucial roles in CNS during health and the injury.
View Article and Find Full Text PDFChaihu-Shugan-San Ameliorated Osteoporosis of Mice with Depressive Behavior Caused by Chronic Unpredictable Mild Stress via Repressing Neuroinflammation and HPA Activity.
Drug Des Devel Ther
December 2024
Spine Disease Research Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People's Republic of China.
Objective: Depression and osteoporosis are usually concurrent health problems. This study aimed to explore the development of osteoporosis in depressive mice model and investigate the beneficial effects of the classical herbal formula Chaihu-Shugan-San (CHSG) on the brain and bone.
Methods: CHSG powder was prepared by spray-drying following extraction with water.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!