Postsynaptic lncRNA Sera/Pkm2 pathway orchestrates the transition from social competition to rank by remodeling the neural ensemble in mPFC DOI Creative Commons
Ling‐Shuang Zhu,

Chuan Lai,

Chao-Wen Zhou

et al.

Cell Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 20, 2024

Individuals' continuous success in competitive interactions with conspecifics strongly affects their social hierarchy. Medial prefrontal cortex (mPFC) is the key brain region mediating both competition and However, molecular regulatory mechanisms underlying neural ensemble mPFC remains unclear. Here, we demonstrate that excitatory neurons of prelimbic (PL), lncRNA Sera remodels utilization Pkm Exon9 Exon10, resulting a decrease Pkm1/2 ratio highly mice. By employing tet-on/off system, disrupt or rebuild normal by controlling expression Pkm2 PL neurons. We find long-term modulation induces timely alteration hysteretic rank change, through phosphorylating Ser845 site GluA1. Together, this study uncovers crucial role Sera/Pkm2 pathway transition to remodeling mPFC.

Language: Английский

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice DOI Creative Commons
Xuan Wang,

Xiaole Tang,

Pengfei Zhu

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: March 13, 2024

Abstract Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer’s due to their covalently closed loop structure. However, involvement circRNAs postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted whole transcriptome sequencing initially this study. According expression profiles, observed that circAKT3 was associated with hippocampal neuronal apoptosis mice. Moreover, found overexpression reduced neurons alleviated POCD. Subsequently, through bioinformatics analysis, our data showed vitro vivo elevated abundance miR-106a-5p significantly, resulting a decrease HDAC4 protein an increase MEF2C protein. Additionally, effect blocked by inhibitor. Interestingly, could activate transcription promoter form positive feedback loop. Therefore, findings revealed more potential modulation ways circRNA-miRNA miRNA-mRNA, providing different directions targets for preclinical studies

Language: Английский

Citations

3
Astrocyte–Neuron Interactions in Alzheimer’s Disease DOI
Clara Muñoz‐Castro, Alberto Serrano‐Pozo

Advances in neurobiology, Journal Year: 2024, Volume and Issue: unknown, P. 345 - 382

Published: Jan. 1, 2024

Language: Английский

Citations

3
Tau Pathology Drives Disease‐Associated Astrocyte Reactivity in Salt‐Induced Neurodegeneration DOI Creative Commons

Tongyu Rui,

He‐Zhou Huang, Kai Zheng

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract Dietary high salt intake is increasingly recognized as a risk factor for cognitive decline and dementia, including Alzheimer’s disease (AD). Recent studies have identified population of disease‐associated astrocytes (DAA)‐like closely linked to amyloid deposition tau pathology in an AD mouse model. However, the presence role these high‐salt diet (HSD) models remain unexplored. In this study, it demonstrated that HSD significantly induces enhanced reactivity DAA‐like hippocampal CA3 region mice, with being critically dependent on neuronal pathology. Neuronal activates adenosine A1R signaling, exacerbating by inhibiting Cers1 pathway, which sustains astrocyte reactivity. Additionally, neurons burdened promote via releasing Proteins Associated Promoting Astrocyte Reactivity (PAPD), Lcn2 playing pivotal role. Knockout or its receptor 24p3R mitigates HSD‐induced DAA neuroinflammation. These findings suggest vicious cycle between driving Targeting Tau‐A1R axis may provide novel therapeutic strategy reducing neuroinflammation deficits.

Language: Английский

Citations

0
The role of protein phosphorylation modifications mediated by iron metabolism regulatory networks in the pathogenesis of Alzheimer’s disease DOI Creative Commons

Fei-Xiang Liu,

Yang Su, K. Shi

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Feb. 25, 2025

Alzheimer's disease (AD) is a severe neurodegenerative characterized mainly by the formation of amyloid beta (Aβ) plaques and abnormal phosphorylation tau. In recent years, an imbalance in iron homeostasis has been recognized to play key role pathological process AD. Abnormal accumulation can activate various kinases such as glycogen synthase kinase-3β, cyclin-dependent kinase 5, mitogen-activated protein kinase, leading tau precursor protein, accelerating Aβ neurofibrillary tangles. addition, iron-mediated oxidative stress not only triggers neuronal damage, but also exacerbates dysfunction altering N-methyl-D-aspartate receptors γ-aminobutyric acid type A receptors. Iron affects status tyrosine hydroxylase, rate-limiting enzyme for dopamine synthesis, interfering with signaling pathway. On other hand, transport metabolism brain regulating transferrin, further disrupting homeostasis. Therapeutic strategies targeting show promise reducing accumulation, inhibiting stress, proteins. This article reviews molecular mechanisms modifications mediated AD, discusses potential interventions that regulate related pathways, providing new theoretical basis treatment

Language: Английский

Citations

0
Identification and Evaluation of Lipocalin-2 in Sepsis-Associated Encephalopathy via Machine Learning Approaches DOI Creative Commons
Jia Hu, Zengze Chen,

Jinyan Wang

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3843 - 3858

Published: March 1, 2025

Sepsis-associated encephalopathy (SAE) critically contributes to poor prognosis in septic patients. Identifying and screening key genes responsible for SAE, as well exploring potential targeted therapies, are vital improving the management of sepsis advancing precision medicine. Single-cell RNA sequencing (scRNA-seq) was administrated identify cell subpopulations related Next, hierarchical dynamic weighted gene co-expression network analysis (hdWGCNA) employed associated with specific neutrophil subpopulations. Enrichment revealed biological functions these genes. Subsequently, neuroinflammation-related were obtained construct a signature. The AddModuleScore algorithm used calculate neuroinflammation scores each subpopulation, whereas CellCall assess crosstalk between neutrophils other To accurately, four binary classification machine learning algorithms utilized. Finally, Western blotting behavioral tests confirm role LCN2-related mice. This study utilized scRNA-seq reveal critical peripheral during sepsis, identifying contributors neuroinflammation. On basis various algorithms, we discovered that Lipocalin-2 (LCN2) may be involved neutrophil-induced SAE. prove findings, conducted vivo experiments an animal model. Increased LCN2 expression cognitive dysfunction occurred Additionally, levels markers astrocytes microglia inflammatory factors such TNF-α IL-6 significantly increased. All phenomena reversed by downregulation LCN2. upregulation on is step triggers central nervous system

Language: Английский

Citations

0
Humanized rodent models of neurodegenerative diseases and other brain disorders DOI
X.B Zhang, Jianxiang Wang, Jiewen Zhang

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 106112 - 106112

Published: March 1, 2025

Language: Английский

Citations

0
MicroRNAs in the biology and hallmarks of neurodegenerative diseases DOI

Shivnarayan Dhuppar,

Wolfram C. Poller, Gopal Murugaiyan

et al.

Trends in Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Engineered Exosomes Improve the Effects of Curcumin on Protecting Mitochondria of Neurons in Alzheimer's Disease DOI Creative Commons

Yaning Ding,

Meiqi Li,

Jiayi Song

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101738 - 101738

Published: April 11, 2025

The synthetic DSPE-PEG2000-C3 peptide and DSPE-PEG2000-TPP were designed to modify the exosomes (EXO) by incubation, through which guide C3/TPP-EXO target injured mitochondria of neurons. Then, was further used encapsulate curcumin (CUR) enhance solubility bioavailability drug. By intravenously injected (i.v) into taup301s mutant transgenic (Tg) mice, facilitated CUR neurons increase entry efficiency medication. To reveal mechanisms drug entry, sodium azide (NaN3), an energy inhibitor, treat HT22 cells. results demonstrated that entrance engineered EXO is significantly affected suggesting may routes. deeply study exact molecular C3/TPP-EXO-CUR in treating AD, RNA-Seq identify relevant molecules. Through GO annotation, many genes are enriched pathways functions. Based on these data, showed neuroprotective effects via modulating protein expression Bcl-2, Bax caspase-3 confirm vitro results, vivo revealed treatment inhibited phosphorylation tau protected inhibiting apoptotic genes, leading improve memory decline mice. Collectively, current benefits for might provide a novel effective therapeutic approach disease.

Language: Английский

Citations

0
Progress of Astrocyte-Neuron Crosstalk in Central Nervous System Diseases DOI
Yi Zhang, Ziyu Wang, Fenglian Xu

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(12), P. 3187 - 3207

Published: Sept. 18, 2024

Language: Английский

Citations

3
Novel Approaches to Studying SLC13A5 Disease DOI Creative Commons
Adriana S. Beltrán

Metabolites, Journal Year: 2024, Volume and Issue: 14(2), P. 84 - 84

Published: Jan. 24, 2024

The role of the sodium citrate transporter (NaCT) SLC13A5 is multifaceted and context-dependent. While aberrant dysfunction leads to neonatal epilepsy, its therapeutic inhibition protects against metabolic disease. Notably, insights regarding cellular molecular mechanisms underlying these phenomena are limited due intricacy complexity latent human physiology, which poorly captured by existing animal models. This review explores innovative technologies aimed at bridging such a knowledge gap. First, I provide an overview variants in context disease specific cell types where expression has been observed. Next, discuss current for generating patient-specific induced pluripotent stem cells (iPSCs) their inherent advantages limitations, followed summary methods differentiating iPSCs into neurons, hepatocytes, organoids. Finally, explore relevance models as platforms delving intricate SLC13A5-related disorders.

Language: Английский

Citations

2