Upregulated inwardly rectifying K⁺ current-mediated hypoactivity of parvalbumin interneuron underlies autism-like deficits in <i>Bod1</i>-deficient mice

Journal of Biomedical Research, Journal Year: 2025, Volume and Issue: 39, P. 1 - 1

Published: Jan. 1, 2025

Parvalbumin-positive (PV +) interneuron dysfunction is believed to be linked autism spectrum disorder (ASD), a neurodevelopmental disorder, characterized by social deficits and stereotypical behaviors. However, the underlying mechanisms of PV + remain largely unclear. Here, we found that deficiency biorientation defective 1 ( Bod1) in led an ASD-like phenotype Pvalb-Cre; Bod1 f/f mice. Mechanistically, identified induced hypoactivity hyperactivity calcium/calmodulin-dependent protein kinase Ⅱ alpha (CaMKⅡα) neurons medial prefrontal cortex (mPFC), as determined whole-cell patch-clamp recording. Additionally, it concurrently decreased power high gamma oscillation, assessed vivo multi-channel electrophysiological Furthermore, enhanced inwardly rectifying K current, leading increase resting membrane potential interneurons. Importantly, gain-of-function improved behaviors These findings provide mechanistic insights into suggest new strategies for developing therapies ASD.

Language: Английский

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Agomelatine Alleviates Depressive-like Behaviors by Suppressing Hippocampal Oxidative Stress in the Chronic Social Defeat Stress Model

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 410 - 410

Published: March 28, 2025

Major depressive disorder (MDD) is a common psychiatric characterized by significant mood disturbances and cognitive impairments. Chronic stress, particularly social defeat plays crucial role in the etiology of depression, with oxidative stress being pivotal factor its pathophysiology. Consequently, identifying effective strategies to mitigate prevent progression depression paramount importance. Agomelatine, an atypical antidepressant melatonergic serotonergic properties, has shown promise treating MDD due unique mechanisms action. In this study, we aimed investigate whether agomelatine could ameliorate behavioral deficits chronic (CSDS) mouse model. CSDS mice were administered (50 mg/kg, intraperitoneally) exhibited reductions both anxiety-like depressive-like behaviors tests. Further analysis revealed that treatment effectively reduced damage hippocampus mice. Additionally, attenuated mitochondrial dysfunction restored synaptic plasticity, as evidenced increased density excitatory synapses enhanced neuronal activity. These findings suggest may exert therapeutic effects reducing preserving function, enhancing providing new insights into potential for stress-induced depression.

Language: Английский

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S‐ketamine Alleviates Neuroinflammation and Attenuates Lipopolysaccharide‐Induced Depression Via Targeting SIRT2

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

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Unraveling the Molecular Underpinnings: The Therapeutic Impact of Aerobic Exercise on Anxiety Disorders

Current Medical Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Language: Английский

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