Ghrelin Inhibits Inflammasomes Activation in Astrocytes, Alleviates Pyroptosis, and Prevents Lipopolysaccharide-induced Depression-like Behavior in Mice DOI Creative Commons
Xiaoou Han,

Xiying Fu,

Wanxu Guo

и другие.

Inflammation, Год журнала: 2024, Номер unknown

Опубликована: Дек. 19, 2024

Depression is the leading cause of disability worldwide and places a significant burden on society. Neuroinflammation closely associated with pathophysiology depression. Increasing evidence suggests that astrocytes, as most abundant glial cells in brain, are involved occurrence development depression due to morphological abnormalities dysfunction. Astrocytes express NOD-like receptor protein 2 (NLRP2) NLRP3 inflammasomes, activation inflammasomes induces pyroptosis. Ghrelin, gastrointestinal peptide, plays vital role regulating inflammation alleviating stress. Therefore, we proposed hypothesis ghrelin inhibits reduces pyroptosis, consequently prevents We used lipopolysaccharide (LPS)-induced mouse model cultured primary astrocytes vitro explore mechanism antidepressant effect ghrelin. Our results showed effectively inhibited acute inflammatory responses damage hippocampus prefrontal cortex. The NLRP2 induced by LPS was significantly Pretreatment suppressed LPS-induced upregulation pyroptosis-related proteins mRNA. Ghrelin alleviated cell membrane pore formation swelling, ultimately improved depression-like behavior. In vitro, prevented mRNA expression initiation assembly NLRP3. exhibits effects, suggesting novel strategy for treating This groundbreaking study reveals new avenues targeting potential therapeutic interventions alleviate

Язык: Английский

Quercetin alleviates chronic unpredictable mild stress‐induced depression‐like behavior by inhibiting NMDAR1 with α2δ‐1 in rats DOI Creative Commons
Mingyan Wang, Xin Wei, Yugai Jia

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(4)

Опубликована: Апрель 1, 2024

Abstract Background Depression is a serious mental disorder and the most prevalent cause of disability suicide worldwide. Chronic unpredictable mild stress (CUMS) can lead to significant acceleration depression development. Quercetin (Que) flavonoid compound with wide range pharmacological effects. Recent studies have shown that quercetin improve CUMS‐induced depression‐like behavior, but mechanism its improvement still unclear. α2δ‐1 regulatory subunit voltage‐gated calcium channel, which interact N‐methyl‐D‐aspartate receptor (NMDAR) form complex. Objective In this study, we found Que could inhibit increase NMDAR expression in rat hypothalamus induced by CUMS. pain, chronic hypertension other interacts complex, subsequently affects level NMDAR. Consequently, present study aimed investigate antidepressant effect vivo vitro explore action terms interaction between Methods Rats were randomly exposed two stressors every day for 4 weeks establish CUMS model, then sucrose preference test (SPT), forced swimming (FST), tail suspension (TST), open field (OFT) performed detect behavior rats, so as evaluate whether model was successfully established on rats. Experimental techniques such serum enzyme‐linked immunosorbent assay (ELISA), immunofluorescence, Western blot, co‐immunoprecipitation, well experiments, used mechanisms exerts Results Behavioral ELISA results showed produce reduction excitability hypothalamic–pituitary–adrenal (HPA) axis rats improvements their depressive behavior. co‐immunoprecipitation experiments produced decrease NMDAR1 levels interfered binding. addition, neural regulation PC12 cells knocked out gene further verified. Cellular demonstrated led reversal up‐regulation corticosterone‐injured cells, while had no effects knockout. Conclusions has good significantly caused It inhibiting α2δ‐1, interfering NMDAR, reducing HPA axis.

Язык: Английский

Процитировано

5

Ferroptosis, pathogenesis and therapy in AS co-depression disease DOI Creative Commons

Yulong Zhao,

Peng Ren,

Qiang Luo

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 24, 2025

Atherosclerosis (AS)-related cardiovascular disease and depression are often comorbid, with patients facing an increased risk of depression, which worsens AS. Both diseases characterized by oxidative stress lipid metabolism disorders. Ferroptosis, a form cell death iron overload harmful peroxide accumulation, is found in various diseases, including AS depression. Consistent the deposition peroxidation (LPO) that characterize ferroptosis mechanism, disturbances also crucial pathogenic mechanisms The comorbid complex, posing challenges for clinical treatment. Chinese herbs hold significant potential owing to their multi-target pharmacological effects. Therefore, this review aims investigate overload, LPO, across types, shared pathogenesis ferroptosis, research on herbal medicine targeting treatment anti-AS co-depression. This provides comprehensive understanding co-depression from perspective ferroptosis.

Язык: Английский

Процитировано

0

Therapeutic Targets and Molecular Mechanisms of Calycosin in the Treatment of Depression: Insights From Chronic Mild Stress Animal Models DOI Creative Commons

Guowei Gong,

Yaqun Liu,

Zhenxia Zhang

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(4)

Опубликована: Апрель 1, 2025

ABSTRACT Background Depression is a complex psychiatric disorder with limited therapeutic options and various side effects. Calycosin, bioactive compound derived from Astragalus membranaceus , possesses multiple pharmacological properties. This study aimed to investigate the antidepressant effects of calycosin in chronic mild stress (CMS) animal models depression elucidate its underlying mechanisms. Methods The were assessed vivo using CMS depression, including grooming frequency test, sucrose intake tail suspension open field test. Neurogenic evaluated by measuring levels BDNF, GDNF, NGF isolated hippocampus tissues. hepatoprotective liver enzyme levels. molecular mechanisms calycosin's explored vitro PC12 cells. Results Calycosin exhibited potent antidepressant‐like activities depression. Treatment significantly alleviated depressive symptoms improved neurogenic Additionally, displayed modulating enzymes vitro. are mediated stimulation TrkB–MEK–Erk1/2–CREB signaling pathway. Conclusion In conclusion, shows promise as novel agent for due diverse Further studies warranted exact targets assess efficacy safety clinical settings.

Язык: Английский

Процитировано

0

Association between triglyceride glucose-body mass index and depression among US adults: A cross-sectional study DOI
Lu Zhang,

Haiyang Sun,

Jiahui Yin

и другие.

Public Health, Год журнала: 2024, Номер 237, С. 410 - 417

Опубликована: Ноя. 11, 2024

Язык: Английский

Процитировано

1

Ghrelin Inhibits Inflammasomes Activation in Astrocytes, Alleviates Pyroptosis, and Prevents Lipopolysaccharide-induced Depression-like Behavior in Mice DOI Creative Commons
Xiaoou Han,

Xiying Fu,

Wanxu Guo

и другие.

Inflammation, Год журнала: 2024, Номер unknown

Опубликована: Дек. 19, 2024

Depression is the leading cause of disability worldwide and places a significant burden on society. Neuroinflammation closely associated with pathophysiology depression. Increasing evidence suggests that astrocytes, as most abundant glial cells in brain, are involved occurrence development depression due to morphological abnormalities dysfunction. Astrocytes express NOD-like receptor protein 2 (NLRP2) NLRP3 inflammasomes, activation inflammasomes induces pyroptosis. Ghrelin, gastrointestinal peptide, plays vital role regulating inflammation alleviating stress. Therefore, we proposed hypothesis ghrelin inhibits reduces pyroptosis, consequently prevents We used lipopolysaccharide (LPS)-induced mouse model cultured primary astrocytes vitro explore mechanism antidepressant effect ghrelin. Our results showed effectively inhibited acute inflammatory responses damage hippocampus prefrontal cortex. The NLRP2 induced by LPS was significantly Pretreatment suppressed LPS-induced upregulation pyroptosis-related proteins mRNA. Ghrelin alleviated cell membrane pore formation swelling, ultimately improved depression-like behavior. In vitro, prevented mRNA expression initiation assembly NLRP3. exhibits effects, suggesting novel strategy for treating This groundbreaking study reveals new avenues targeting potential therapeutic interventions alleviate

Язык: Английский

Процитировано

0