ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
S-ketamine Alleviates Neuroinflammation and Attenuates Lipopolysaccharide-Induced Depression Via Targeting SIRT2.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- The sirtuin family: from mechanisms to therapy.Molecular biomedicine · 2026Review
- Molecular Editing Reveals a Bilobalide Chemotype that Attenuates Prolyl Endopeptidase (PREP)-Linked Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Low Dose Ketamine Preconditions Astrocyte Mitochondria to Achieve Antidepressant Efficacy via Adenosine, Humanin, and Melatonin Upregulation and Efflux.Alpha psychiatry · 2026Article
- TrkB promotes the neuronal secretion of soluble Siglec-2 (CD22) to mitigate microglial activation and alleviate depression-like behaviors in male mice.Molecular psychiatry · 2026Article
- A Novel Approach to Neuropathic Pain Treatment: Lactylation Targeting Microglia.Molecular neurobiology · 2026Review
- SirT2 Inhibition is Associated with Improvements in Depression-like Behavior and Memory Impairment in Olfactory Bulbectomized Mice.Molecular neurobiology · 2026Article
- Targeting γ-aminobutyric acid type A receptors to mitigate perioperative neurocognitive disorders: a narrative review.British journal of anaesthesia · 2026Review
- Clinical research progress of esketamine in perioperative neuroprotection: from mechanisms to therapeutic neuroprotection.Frontiers in pharmacology · 2026Review
- Xiaoyao San against depression via glia-mediated neuroinflammation using network pharmacology and experimental validation.Scientific reports · 2025Article
- Nomilin Regulates Depressive-Like Behaviors in Mice via the Ventral Part of the Lateral Septum to Bed Nucleus of the Stria Terminalis Circuit.CNS neuroscience & therapeutics · 2025Article
- Pregabalin and Duloxetine in Patients with Non-Nociceptive Pain: A Narrative Review Exploring the Pharmacological Effects of This Combination.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Ketamine's Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- S-ketamine Alleviates Neuroinflammation and Attenuates Lipopolysaccharide-Induced Depression Via Targeting SIRT2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
8 authors.
Funding
Abstract
Depression, a pervasive mental health condition, has increasingly been linked to neuroinflammation, as evidenced by elevated levels of pro-inflammatory markers such as TNF-α and IL-1β observed in patients, which underscores the role of inflammation in its pathophysiology. This study investigates the differential effects of S-ketamine (S-KET) and R-ketamine (R-KET) on inflammation-induced depression using a lipopolysaccharide (LPS)-induced mouse model. Results showed that S-KET, but not R-KET, significantly alleviated depressive-like behaviors and reduced levels of pro-inflammatory factors in the medial prefrontal cortex (mPFC). Activity-based protein profiling identified SIRT2 as a key intracellular target of S-KET, with direct binding observed at the Q167 residue, whereas R-KET showed no such binding. S-KET enhanced SIRT2 interaction with NF-κB subunit p65, reducing its acetylation and suppressing pro-inflammatory gene expression, effects not seen with R-KET. In vitro studies with RNA interference and the SIRT2 inhibitor AK-7, along with in vivo pharmacological blockade, confirmed that SIRT2 is crucial for the anti-inflammatory and antidepressant actions of S-KET. These findings suggest that SIRT2 mediates the therapeutic effects of S-KET, highlighting its potential as a target for treating inflammation-associated depression. This study provides novel insights into the stereospecific actions of ketamine enantiomers and the promise of targeting SIRT2 for neuroinflammatory depression.
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