Deferoxamine alleviates ferroptosis in seawater immersion combined with traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, with its severity potentially exacerbated by seawater immersion. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has been implicated in TBI pathogenesis. However, the specific occurrence and underlying mechanisms of ferroptosis in the context of TBI compounded by seawater immersion remain unclear.

Macrophagic HDAC3 inhibition ameliorates Dextran Sulfate Sodium induced inflammatory bowel disease through GBP5-NLRP3 pathway.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease, characterized by dysregulated immune response. HDAC3 is reported to be an epigenetic brake in inflammation, playing critical roles in macrophages. However, its role in IBD is unclear.

Extracellular Matrix Remodeling Alleviates Memory Deficits in Alzheimer's Disease by Enhancing the Astrocytic Autophagy-Lysosome Pathway.

Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short-term memory loss and reduced amyloid-beta (Aβ) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aβ plaques, and enhanced astrocyte recruitment to surrounding plaques.

PRRC2B modulates oligodendrocyte progenitor cell development and myelination by stabilizing Sox2 mRNA.

Oligodendrocyte progenitor cells (OPCs) differentiate into myelin-producing cells and modulate neuronal activity. Defects in OPC development are associated with neurological diseases. N-methyladenosine (mA) contributes to neural development; however, the mechanism by which mA regulates OPC development remains unclear.

Acute ischemia induces spatially and transcriptionally distinct microglial subclusters.

Background: Damage in the ischemic core and penumbra after stroke affects patient prognosis. Microglia immediately respond to ischemic insult and initiate immune inflammation, playing an important role in the cellular injury after stroke. However, the microglial heterogeneity and the mechanisms involved remain unclear.

CALHM2 V136G polymorphism reduces astrocytic ATP release and is associated with depressive symptoms and Alzheimer's disease risk.

Introduction: Depression is considered a prodromal state of Alzheimer's disease (AD), yet the underlying mechanism(s) by which depression increases the risk of AD are not known.

Methods: Single-nucleotide polymorphism (SNP) analysis was used to determine the CALHM2 variants in AD patients. Cellular and molecular experiments were conducted to investigate the function of CALHM2 V136G mutation.

Lactate metabolism in neurodegenerative diseases.

Lactate, a byproduct of glycolysis, was thought to be a metabolic waste until the discovery of the Warburg effect. Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions. The Astrocyte-Neuron Lactate Shuttle has clarified that lactate plays a pivotal role in the central nervous system.

Noncanonical contribution of microglial transcription factor NR4A1 to post-stroke recovery through TNF mRNA destabilization.

Microglia-mediated neuroinflammation is involved in various neurological diseases, including ischemic stroke, but the endogenous mechanisms preventing unstrained inflammation is still unclear. The anti-inflammatory role of transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) in macrophages and microglia has previously been identified. However, the endogenous mechanisms that how NR4A1 restricts unstrained inflammation remain elusive.

The Role of PRRC2B in Cerebral Vascular Remodeling Under Acute Hypoxia in Mice.

High altitude exposure leads to various cognitive impairments. The cerebral vasculature system plays an integral role in hypoxia-induced cognitive defects by reducing oxygen and nutrition supply to the brain. RNA N6-methyladenosine (m6A) is susceptible to modification and regulates gene expression in response to environmental changes, including hypoxia.

PVT1 alleviates hypoxia-induced endothelial apoptosis by enhancing autophagy via the miR-15b-5p/ATG14 and miR-424-5p/ATG14 axis.

Endothelial dysfunction plays a crucial role in the pathogenesis of vascular disease. Long noncoding RNA (lncRNA) and microRNA (miRNA) play important roles in various cellular processes and are involved in several vascular endothelial cells (VECs) biological processes, including cell growth, migration, autophagy, and apoptosis. The functions of plasmacytoma variant translocation 1 (PVT1) in VECs have been progressively investigated in recent years, mainly with regard to proliferation and migration of endothelial cells (ECs).

P2X7 receptor-mediated depression-like reactions arising in the mouse medial prefrontal cortex.

Major depressive disorder is a frequent and debilitating psychiatric disease. We have shown in some of the acute animal models of major depressive disorder (tail suspension test and forced swim test) that depression-like behavior can be aggravated in mice by the microinjection into the medial prefrontal cortex of the P2X7R agonistic adenosine 5'-triphosphate or its structural analog dibenzoyl-ATP, and these effects can be reversed by the P2X7R antagonistic JNJ-47965567. When measuring tail suspension test, the prolongation of immobility time by the P2YR agonist adenosine 5'-[β-thio]diphosphate and the reduction of the adenosine 5'-(γ-thio)triphosphate effect by P2Y1R (MRS 2179) or P2Y12R (PSB 0739) antagonists, but not by JNJ-47965567, all suggest the involvement of P2YRs.

Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia.

Neuroinflammation is involved in the development of Parkinson's disease (PD). Calhm2 plays an important role in the development of microglial inflammation, but whether Calhm2 is involved in PD and its regulatory mechanisms are unclear. To study the role of Calhm2 in the development of PD, we utilized conventional Calhm2 knockout mice, microglial Calhm2 knockout mice and neuronal Calhm2 knockout mice, and established the MPTP-induced PD mice model.

deletion in microglia ameliorates chronic restraint stress induced mice depression-like behavior.

Major depression is one of the most common psychiatric disorders worldwide, inflicting suffering, significant reduction in life span, and financial burdens on families and society. Mounting evidence implicates that exposure to chronic stress can induce the dysregulation of the immune system, and the activation of brain-resident innate immune cells, microglia, leading to depression-like symptoms. However, the specific mechanisms need to be further elucidated.

MicroRNA schizophrenia: Etiology, biomarkers and therapeutic targets.

The three sets of symptoms associated with schizophrenia-positive, negative, and cognitive-are burdensome and have serious effects on public health, which affects up to 1% of the population. It is now commonly believed that in addition to the traditional dopaminergic mesolimbic pathway, the etiology of schizophrenia also includes neuronal networks, such as glutamate, GABA, serotonin, BDNF, oxidative stress, inflammation and the immune system. Small noncoding RNA molecules called microRNAs (miRNAs) have come to light as possible participants in the pathophysiology of schizophrenia in recent years by having an impact on these systems.

Nao Tan Qing ameliorates Alzheimer's disease-like pathology by regulating glycolipid metabolism and neuroinflammation: A network pharmacology analysis and biological validation.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and currently there are no available treatments. Alongside the conventional Aβ and tau hypotheses, neuroinflammation and metabolism disruption have also been regarded as crucial hallmarks of AD. In this study, a novel Chinese formula Nao Tan Qing (NTQ) was developed and shown to improve AD.

Microglial hexokinase 2 deficiency increases ATP generation through lipid metabolism leading to β-amyloid clearance.

Microglial cells consume adenosine triphosphate (ATP) during phagocytosis to clear neurotoxic β-amyloid in Alzheimer's disease (AD). However, the contribution of energy metabolism to microglial function in AD remains unclear. Here, we demonstrate that hexokinase 2 (HK2) is elevated in microglia from an AD mouse model (5xFAD) and AD patients.

The role and regulatory mechanism of mA methylation in the nervous system.

N6-methyladenosine (mA) modification regulates RNA translation, splicing, transport, localization, and stability at the post-transcriptional level. The mA modification has been reported to have a wide range of effects on the nervous system, including neurogenesis, cerebellar development, learning, cognition, and memory, as well as the occurrence and development of neurological disorders. In this review, we aim to summarize the findings on the role and regulatory mechanism of mA modification in the nervous system, to reveal the molecular mechanisms of neurodevelopmental processes, and to promote targeted therapy for nervous system-related diseases.

Associations of Sleep Disorders With Depressive Symptoms in Early and Prodromal Parkinson's Disease.

Background: Non-motor symptoms, including sleep disorders and depression, are common in Parkinson's disease (PD). The purpose of our study is to explore the effect of sleep disorders, including the probable rapid eye movement (REM) sleep behavior disorder (pRBD) and the daytime sleepiness, on depressive symptoms in patients with early and prodromal PD.

Methods: A total of 683 participants who obtained from the Parkinson Progression Markers Initiative (PPMI) were included, consisting of 423 individuals with early PD, 64 individuals with prodromal PD, and 196 healthy controls (HCs), who were followed up to 5 years from baseline.

DJ-1 governs airway progenitor cell/eosinophil interactions to promote allergic inflammation.

Background: DJ-1 is an antioxidant protein known to regulate mast cell-mediated allergic response, but its role in airway eosinophilic interactions and allergic inflammation is not known.

Objective: The aim of this study was to investigate the role of DJ-1 in airway eosinophilic inflammation in vitro and in vivo.

Methods: Ovalbumin-induced airway allergic inflammation was established in mice.

The XPO1 Inhibitor KPT-8602 Ameliorates Parkinson's Disease by Inhibiting the NF-κB/NLRP3 Pathway.

Exportin 1 (XPO1) is an important transport receptor that mediates the nuclear export of various proteins and RNA. KPT-8602 is a second-generation inhibitor of XPO1, demonstrating the lowest level of side effects, and is currently in clinical trials for the treatment of cancers. Previous studies suggest that several first-generation inhibitors of XPO1 demonstrate anti-inflammation activities, indicating the application of this drug in inflammation-related diseases.

Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer's disease.

The pro-inflammatory activation of microglia is a hallmark of Alzheimer's disease (AD), and this process involves a switch from oxidative phosphorylation (OXPHOS) toward glycolysis. Here, we show how a positive feedback loop in microglia drives AD pathogenesis, and we demonstrate that inhibiting this cycle in microglia can ameliorate Aβ burden and cognitive deficits in an AD mouse model (5XFAD). After first detecting elevated histone lactylation in brain samples from both 5XFAD mice and individuals with AD, we observed that H4K12la levels are elevated in Aβ plaque-adjacent microglia.