Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Feb. 7, 2022

The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory neuroprotective properties. However, its role potential molecular mechanisms in depression remain unclear. present study aimed to investigate antidepressant activity EDA underlying mechanisms.A chronic social defeat (CSDS) model was performed explore whether could produce effects. Behaviors tests were carried out examine depressive, anxiety-like cognitive behaviors interaction (SI) test, sucrose preference test (SPT), open field (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension (TST) forced swim (FST). Hippocampal medial prefrontal cortex (mPFC) tissues collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), measurement MDA, SOD, GSH, GSH-PX, T-AOC transmission electron microscopy (TEM). Western blotting (WB) quantitative real-time polymerase chain reaction (qRT-PCR) detected Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. EX527, Sirt1 inhibitor ML385, Nrf2 injected intraperitoneally 30 min before injection daily. Knockdown experiments determine effects Gpx4 on CSDS mice with treatment by an adeno-associated virus (AAV) vector containing miRNAi (Gpx4)-EGFP infusion.The administrated dramatically ameliorated CSDS-induced depressive behaviors. In addition, notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, damage, metabolism pro-inflammatory cytokines activation hippocampus (Hip) mPFC mice. Further examination indicated that application after significantly increased protein expressions Sirt1, Nrf2, HO-1 Hip. EX527 abolished effect as well levels Gpx4. Similarly, ML385 reversed anxiolytic via decreased knockdown EDA-generated efficacy behaviors.These findings suggest possesses potent properties through axis Gpx4-mediated ferroptosis may play key this effect.

Language: Английский

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Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Jan. 17, 2022

The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate regimen that mimics the metabolism of fasting state to induce production ketone bodies. KD has long been established as remarkably successful dietary approach for treatment intractable epilepsy increasingly garnered research attention rapidly in past decade, subject emerging evidence promising therapeutic potential various diseases, besides epilepsy, from obesity malignancies. In this review, we summarize experimental and/or clinical efficacy safety different discuss possible mechanisms action based on recent advances understanding influence at cellular molecular levels. We emphasize may function through multiple mechanisms, which remain be further elucidated. challenges future directions implementation spectrum diseases have discussed. suggest that, with encouraging effects increasing insights into action, randomized controlled trials should conducted elucidate foundation use KD.

Language: Английский

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Neuroinflammation induces anxiety- and depressive-like behavior by modulating neuronal plasticity in the basolateral amygdala

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 91, P. 505 - 518

Published: Nov. 6, 2020

Language: Английский

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Microglia in depression: current perspectives

Science China Life Sciences, Journal Year: 2020, Volume and Issue: 64(6), P. 911 - 925

Published: Oct. 14, 2020

Language: Английский

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Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 92, P. 10 - 24

Published: Nov. 10, 2020

Language: Английский

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The ATP Level in the Medial Prefrontal Cortex Regulates Depressive-like Behavior via the Medial Prefrontal Cortex-Lateral Habenula Pathway

Biological Psychiatry, Journal Year: 2022, Volume and Issue: 92(3), P. 179 - 192

Published: Feb. 22, 2022

Language: Английский

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Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 9, 2023

Abstract Alterations in energy metabolism are associated with depression. However, the role of glycolysis pathogenesis depression and underlying molecular mechanisms remain unexplored. Through an unbiased proteomic screen coupled biochemical verifications, we show that levels lactate dehydrogenase A (LDHA), a glycolytic enzyme catalyzes L-lactate production, reduced dorsomedial prefrontal cortex (dmPFC) stress-susceptible mice chronic social defeat stress (CSDS) model. Conditional knockout LDHA from brain promotes depressive-like behaviors both male female mice, accompanied decreased neuronal excitability dmPFC. Moreover, these phenotypes could be duplicated by knockdown dmPFC or specifically astrocytes. In contrast, overexpression reverses phenotypic changes CSDS-susceptible mice. Mechanistic studies demonstrate through monocarboxylic acid transporter 2 (MCT2) inhibiting large-conductance Ca 2+ -activated potassium (BK) channel. Together, results reveal maintaining to prevent behaviors.

Language: Английский

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Mitochondrial dysfunction: A fatal blow in depression

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115652 - 115652

Published: Oct. 4, 2023

Mitochondria maintain the normal physiological function of nerve cells by producing sufficient cellular energy and performing crucial roles in maintaining metabolic balance through intracellular Ca2+ homeostasis, oxidative stress, axonal development. Depression is a prevalent psychiatric disorder with an unclear pathophysiology. Damage to hippocampal neurons key component plasticity regulation synapses plays critical role mechanism depression. There evidence suggesting that mitochondrial dysfunction associated synaptic impairment. The maintenance homeostasis includes quantitative quality control mitochondria. Mitochondrial biogenesis produces new healthy mitochondria, dynamics cooperates mitophagy remove damaged These processes population stability exert neuroprotective effects against early In contrast, observed various brain regions patients major depressive disorders. accumulation defective mitochondria accelerates dysfunction. addition, impaired aggravate alterations microenvironment, promoting neuroinflammation depletion, thereby exacerbating development This review summarizes influence underlying molecular pathways on pathogenesis Additionally, we discuss as potential therapeutic strategy for

Language: Английский

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Microglia: A Central Player in Depression

Current Medical Science, Journal Year: 2020, Volume and Issue: 40(3), P. 391 - 400

Published: June 1, 2020

Summary Microglia are the major immune cells in central nervous system and play a key role normal function of brain. exhibit functional diversity, they control inflammation through releasing inflammatory cytokine, clearing apoptotic via phagocytosis, regulating synaptic plasticity formation neural network by synapse pruning. Recent studies have strongly indicated that microglial dysfunction is associated with variety neuropsychiatric diseases such as depression, which been termed “microgliopathy”. The emergency advanced technologies tools has enabled us to comprehensively understand microglia physiology pathology, growing targetted explore treatment diseases. Here, we describe progress research, review recent developments understanding etiology depression.

Language: Английский

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The Therapeutic Role of Ketogenic Diet in Neurological Disorders

Nutrients, Journal Year: 2022, Volume and Issue: 14(9), P. 1952 - 1952

Published: May 6, 2022

The ketogenic diet (KD) is a high-fat, low-carbohydrate and adequate-protein that has gained popularity in recent years the context of neurological diseases (NDs). complexity pathogenesis these means effective forms treatment are still lacking. Conventional therapy often associated with increasing tolerance and/or drug resistance. Consequently, more therapeutic strategies being sought to increase effectiveness available improve quality life patients. For moment, it seems KD can provide benefits patients problems by effectively controlling balance between pro- antioxidant processes pro-excitatory inhibitory neurotransmitters, modulating inflammation or changing composition gut microbiome. In this review we evaluated potential efficacy epilepsy, depression, migraine, Alzheimer’s disease Parkinson’s disease. our opinion, should be considered as an adjuvant option for some diseases.

Language: Английский

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