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

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 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

Язык: Английский

Unraveling the Pathogenesis of Post‐Stroke Depression in a Hemorrhagic Mouse Model through Frontal Lobe Circuitry and JAK‐STAT Signaling DOI Creative Commons

Ying-Qing Wu,

Jia Deng,

Jinsong Ma

и другие.

Advanced Science, Год журнала: 2024, Номер 11(33)

Опубликована: Июль 1, 2024

Post-stroke depression is a common complication that imposes significant burdens and challenges on patients. The occurrence of often associated with frontal lobe hemorrhage, however, current understanding the underlying mechanisms remains limited. Here, pathogenic circuitry connectivity, electrophysiological alterations, molecular characteristics are investigated related to in adult male mice following unilateral injection blood medial prefrontal cortex (mPFC). It demonstrated specific neurological hematoma model mPFC, ventral tegmental area (VTA) shows higher percentage connectivity disruption compared lateral habenula (LHb) striatum (STR). Additionally, long-range projections originating from demonstrate damage percentages within connections between each region mPFC. mPFC neurons reveal reduced neuronal excitability altered synaptic communication. Furthermore, transcriptomic analysis identifies involvement Janus Kinase-Signal Transducer Activator Transcription (JAK-STAT) signaling pathway, targeting JAK-STAT pathway significantly alleviates severity depressive symptoms. These findings improve post-hemorrhagic may guide development efficient treatments.

Язык: Английский

Процитировано

3
Investigating the Potential Therapeutic Targeting of the JAK-STAT Pathway in Cerebrovascular Diseases: Opportunities and Challenges DOI
Jiawei Wu, Bingxin Wang,

Li-Ping Shen

и другие.

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Язык: Английский

Процитировано

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

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 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

Язык: Английский

Процитировано

0