Echinacoside exerts antidepressant-like effects through enhancing BDNF-CREB pathway and inhibiting neuroinflammation via regulating microglia M1/M2 polarization and JAK1/STAT3 pathway

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 4, 2023

The present study was performed to investigate the antidepressant effect of echinacoside (ECH) using chronic unpredictable mild stress (CUMS) induced depression mice and lipopolysaccharide (LPS)-stimulated N9 microglial cells. CUMS treatment on C57BL/6 for 28 days, followed by gavaging with different doses (15 60 mg/kg) 21 consecutive days. Sucrose preference test (SPT), open field (OFT), tail suspension (TST), forced swimming (FST) were measured assess effects CUMS-Induced Depressive-Like Behaviors. After that, pathological changes hippocampus determined Hematoxylin eosin (HE) staining Nissl staining; neurotransmitters, pro-inflammatory cytokines indoleamine 2,3-dioxygenase (IDO) levels, hypothalamic-pituitary-adrenal (HPA) axis activity enzyme linked immunosorbent assay (ELISA); Iba 1were evaluated Immunofluorescence assay; Key protein expression levels CREB/BDNF signal pathway western blotting. Subsequently, cells stimulated 1 μg/ml LPS induce microglia activation, treated 5-20 μM 24 h. NO, interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), IL-4, IL-10, transforming growth beta (TGF-β) in cell culture supernatants enzyme-linked (ELISA) kits; morphology level observed high-content screening M1 markers CD11b, CD86 M2 CD206 analyzed imaging flow cytometry. Results show that reversed CUMS-increased immobility time OFT, TST, FST CUMS-reduced sucrose SPT. In addition, reduced 1. Moreover, significantly increased p-CREB/CREB ratio BDNF hippocampus. Furthermore, secretion inflammatory factors inhibited polarization conclusion, may be beneficial diseases through regulating balance inhibiting phenotype, improving hippocampal neurogenesis CREB-BDNF signaling pathway.

Language: Английский

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Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex

Pharmacological Research, Journal Year: 2023, Volume and Issue: 191, P. 106717 - 106717

Published: March 21, 2023

Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons well understood, which can alleviate inflammation. Nevertheless, potential effects Nr4a2 on neuroinflammation depression still remains unclear. Chronic lipopolysaccharides (LPS) stress induced depressive-behaviors were confirmed via behavioral tests. Differentially expressed genes detected by using RNA-sequencing. anterior cingulate cortex (ACC) tissues collected for biochemical experiments. Golgi-Cox staining and virus labeling used to evaluate the dendritic spines. We applied fluoxetine (FLX) amodiaquine dihydrochloride (AQ, a highly selective agonist Nr4a2) mice. Overexpression experiments performed injecting AAV-Nr4a2-EGFP into ACC. Chemogenetic activation CamkII hM3Dq virus. Mice treated LPS displayed depressive- anxiety-like behaviors. reduction FosB rescued pretreatment FLX or AQ. More importantly, LPS-induced behavior deficits mice alleviated treatment pharmacological expression Nr4a2. Meanwhile, enhancing level could improve spines loss neuron morphological changes microglia. ACC reversed behaviors caused administration. Activation robustly increase deficits. Our findings demonstrate that may regulate depressive-like alleviating impairment morphology function microglia chronic neuroinflammation.

Language: Английский

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The microglial innate immune receptors TREM-1 and TREM-2 in the anterior cingulate cortex (ACC) drive visceral hypersensitivity and depressive-like behaviors following DSS-induced colitis

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 112, P. 96 - 117

Published: June 5, 2023

Language: Английский

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Understanding the Role of Oxidative Stress, Neuroinflammation and Abnormal Myelination in Excessive Aggression Associated with Depression: Recent Input from Mechanistic Studies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 915 - 915

Published: Jan. 4, 2023

Aggression and deficient cognitive control problems are widespread in psychiatric disorders, including major depressive disorder (MDD). These abnormalities known to contribute significantly the accompanying functional impairment global burden of disease. Progress development targeted treatments excessive aggression symptoms has been limited, there exists a unmet need develop more efficacious for depressed patients. Due complex nature clinical heterogeneity MDD lack precise knowledge regarding its pathophysiology, effective management is challenging. Nonetheless, aetiology pathophysiology subject extensive research vast body latest literature that points new mechanisms this disorder. Here, we overview key mechanisms, which include neuroinflammation, oxidative stress, insulin receptor signalling abnormal myelination. We discuss hypotheses have proposed unify these processes, as many pathways integrated neurobiology MDD. also describe current translational approaches modelling depression, recent advances stress models MDD, emerging novel therapies, aggression, such anti-diabetic drugs, antioxidant treatment herbal compositions.

Language: Английский

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Integrating spatial and single-nucleus transcriptomic data elucidates microglial-specific responses in female cynomolgus macaques with depressive-like behaviors

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(8), P. 1352 - 1364

Published: July 13, 2023

Language: Английский

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