α-Synuclein (α-Syn), a pathological hallmark of Parkinson's disease (PD), has been recognized to induce the production interleukin-1β in process that depends, at least vitro, on nod-like receptor protein 3 (NLRP3) inflammasome monocytes. However, role NLRP3 activation onset PD not yet fully established. In this study, we showed inflammasomes were activated serum patients and midbrain model mice. We further clarified α-syn through microglial endocytosis subsequent lysosomal cathepsin B...

Abnormal aggregation of brain α-synuclein is a central step in the pathogenesis Parkinson's disease (PD), thus, it reliable to promote clearance prevent and treat PD. Recent studies have revealed an essential role glymphatic system meningeal lymphatic vessels macromolecules, however, their pathophysiological aspects remain elusive.Meningeal drainage 18-week-old A53T mice was blocked via ligating deep cervical lymph nodes. Six weeks later, functions PD-like phenotypes were systemically...

Abstract Background Senescent astrocytes play crucial roles in age-associated neurodegenerative diseases, including Parkinson’s disease (PD). Metformin, a drug widely used for treating diabetes, exerts longevity effects and neuroprotective activities. However, its effect on astrocyte senescence PD remains to be defined. Methods Long culture-induced replicative model 1-methyl-4-phenylpyridinium/α-synuclein aggregate-induced premature model, mouse of were investigate the metformin vivo vitro....

Emerging evidence indicates that NLRP3 inflammasome-induced inflammation plays a crucial role in the pathogenesis of depression. Thus, inhibition inflammasome activation may offer therapeutic benefit treatment Fluoxetine, widely used antidepressant, has been shown to have potential antiinflammatory activity, but underlying mechanisms remain obscure.We chronic mild stress model and cultured primary macrophage/microglia investigate effects fluoxetine on its mechanisms.We demonstrated...

Abstract Background Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson’s disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge exerts anti-inflammatory longevity effects neuroprotective activities. However, its effect on astrocyte senescence PD remains to be defined. Methods Long culture-induced replicative model...

Summary Aim Ginkgolide B (GB) has shown neuroprotective effect in treating ischemic stroke, related to its property of anti‐inflammation. Nevertheless, it is unclear whether GB able modulate microglia/macrophage polarization, which recently been proven be vital the pathology stroke. Methods We performed transient middle cerebral artery occlusion (tMCAO) on C57BL/6J male mice and induced cultured BV2 microglia primary bone marrow‐derived macrophages M1/2 phenotype by LPS+ interferon‐γ IL‐4,...

Abstract Classical activation (M1 phenotype) and alternative (M2 are the two polars of microglial states that can produce either neurotoxic or neuroprotective effects in immune pathogenesis Parkinson’s disease (PD). Exploiting beneficial properties microglia cells by modulating their polarization provides great potential for treatment PD. However, mechanism regulates remains elusive. Here we demonstrated Kir6.1-containing ATP-sensitive potassium (Kir6.1/K-ATP) channel switched from...

ATP-sensitive potassium (K-ATP) channels, coupling cell metabolism to membrane potential, are involved in brain diseases, including Parkinson's disease (PD). Kir6.1, a pore-forming subunit of K-ATP channel, is prominently expressed astrocytes and participates regulating its function. However, the precise role astrocytic Kir6.1-contaning channel (Kir6.1/K-ATP) PD not well characterized. In this study, Kir6.1 knockout (KO) mice were used examine effect Kir6.1/K-ATP on dopaminergic (DA)...

Leonurine is an active alkaloid that extracted from Traditional Chinese Medicine Herba leonuri. Emerging evidence indicates leonurine produces neuroprotective effects in ischemic stroke, Parkinson's disease, and Alzheimer's disease. However, the effect of neuropsychiatric disorders, especially major depression, remains unknown. We used chronic mild stress mouse model to explore antidepressant potential mechanisms. Behavioral tests including sucrose preference test, forced swimming tail...

α-Synuclein (α-Syn)-induced neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Dopamine D2 receptor (Drd2) has been regarded as potential anti-inflammatory target therapy neurodegenerative diseases. However, effect astrocytic Drd2 α-Syn-induced remains unclear.The on was examined mouse primary astrocyte vitro and A53T transgenic mice vivo. The inflammatory responses were detected using immunofluorescence, ELISA, qRT-PCR. details molecular mechanism...

Rationale: Astrocyte dysfunction is one of the important pathological mechanisms depression. Stress contributes to onset As metabolic stress sensor, Kir6.1-contaning K-ATP channel (Kir6.1/K-ATP) prominently expressed in astrocytes. However, involvement Kir6.1/K-ATP depression remains obscure. Methods: Astrocyte-specific Kir6.1 knockout mice were used prepare two mouse models explore role astrocytic Primary astrocytes cultured reveal underlying mechanism for Kir6.1-regulated pyroptosis....

Cross-talk between the nervous and immune systems is involved in neurological diseases. However, their potential interplay depression has yet to be elucidated. Here, using single-cell RNA neutrophil SMART sequencing, we showed that CCR5 + neutrophils were significantly increased patients with preferentially migrated hippocampus a mouse model of depression. Infiltrated engulf neuronal spines subsequently promote depressive symptoms male mice. Furthermore, by genetic or pharmacologic...

Resveratrol is a natural compound that affects energy metabolism and also known to possess an array of cardioprotective effects. However, its overall effects on the underlying mechanism involved in cardioprotection require further investigation. Herein we hypothesize ATP-sensitive potassium (K-ATP) channels as molecular sensors cellular may mediate resveratrol. Kir6.2 knockout, Kir6.1 heterozygous wild-type (WT) mice were subjected ischemia/reperfusion injury injected with resveratrol (10...

Previous research has demonstrated that ClC-3 is responsible for volume-regulated Cl-current (ICl.vol) in vascular smooth muscle cells (VSMCs). However, it still not clear whether and how transported to cell membranes, resulting alteration ofICl.vol.Methods Results:Volume-regulated chloride current was recorded by whole-cell patch clamp recording, Western blotting co-immunoprecipitation were performed examine protein expression protein-protein interaction. Live imaging used observe...

Abstract Objectives We have previously found that volume-regulated chloride current (VRCC) is involved in cell cycle progression and proliferation. This study was to examine the effect of Tween 80, a nonionic surfactant, on VRCC proliferation rat basilar artery smooth muscle cells (BASMCs). Methods recorded using whole-cell patch clamp. Cell were determined by CCK-8, count flow cytometry. Key findings The results showed endothelin-1 promotes transition from G0/G1 phase S significantly...