Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation DOI Creative Commons

Amelia Pizzella,

Eduardo Penna, Yan Liu

et al.

Progress in Neurobiology, Journal Year: 2024, Volume and Issue: 242, P. 102684 - 102684

Published: Oct. 30, 2024

Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by motor disfunction, seizures, intellectual disability, speech deficits, and autism-like behavior, showing high comorbidity with Autism Spectrum Disorders (ASD). It known that stimulation of the serotonin receptor 7 (5-HT7R) can rescue some behavioral neuroplasticity dysfunctions in animal models Fragile X Rett syndrome, two pathologies associated ASD. In view these observations, we hypothesised alterations 5-HT7R signalling might also be involved AS. To test this hypothesis, stimulated selective agonist LP-211 to investigate its possible beneficial effects on synaptic altered behavior AS mice model. mutant mice, observed impairment machinery protein synthesis, which was reversed activation. Moreover, able to: i) enhance dendritic spine density hippocampal neurons, reduced mice; ii) restore impaired long-term potentiation (LTP) slices iii) improve cognitive performance animals subjected fear conditioning paradigm. Altogether, our results, restoring molecular deficits AS, suggest targeting could promising therapeutic approach for pathology.

Language: Английский

SARS-CoV-2, COVID-19 and the aging immune system DOI Creative Commons
Juliet M. Bartleson, Dina Radenković, Anthony J. Covarrubias

et al.

Nature Aging, Journal Year: 2021, Volume and Issue: 1(9), P. 769 - 782

Published: Sept. 14, 2021

Language: Английский

Citations

283
PI3K/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression DOI Creative Commons
Ningning Guo, Xin Wang,

Muran Xu

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107300 - 107300

Published: July 9, 2024

Depression is a serious global mental disorder. Numerous studies have found that depression may be closely related to decreased neurogenesis, neuroinflammation, neurotransmitter imbalance, and synaptic plasticity dysfunction. The pathogenesis of complex involves multiple signal transduction pathways molecular changes. PI3K/AKT pathway an essential signaling in neurons, which widely expressed emotion-related regions the brain. Therefore, play moderating role mood disorders. However, mechanism not been fully described. This review systematically summarized discussed its potential treatment depression. will help development antidepressants.

Language: Английский

Citations

23
Oxytocin alleviates cognitive and memory impairments by decreasing hippocampal microglial activation and synaptic defects via OXTR/ERK/STAT3 pathway in a mouse model of sepsis-associated encephalopathy DOI
Junliang Jiang, Yue Zou, Chuantong Xie

et al.

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 114, P. 195 - 213

Published: Aug. 28, 2023

Language: Английский

Citations

26
Developmental deficits, synapse and dendritic abnormalities in a Clcn4 KO autism mice model: endophenotypic target for ASD DOI Creative Commons

Seong Mi Lee,

Yura Choi,

Dayeon Kim

et al.

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 25, 2025

Autism spectrum disorder (ASD) is linked to ion channel dysfunction, including chloride voltage-gated channel-4 (CLCN4). We generated Clcn4 knockout (KO) mice by deleting exon 5 of chromosome 7 in the C57BL/6 mice. KO exhibited reduced social interaction and increased repetitive behaviors assessed using three-chamber marble burying tests. Surprisingly, these symptoms were improved Risperidone treatment, a drug commonly used treat ASD. RNA sequencing data from mouse neural progenitor cells (mNPCs) showed that genes regulating trans-synaptic signaling, transmembrane transport, neuronal projection development significantly decreased knockdown (KD) compared wild type (WT). Moreover, treatment related membrane potential, neuron KD. Abnormalities synaptic plasticity dendritic spine formation also observed WT. phosphorylation SYNAPSIN, PSD95, ERK CREB, as well expression CDK5, brains In cortical neurons, SYNAPSIN PSD95 expressions WT, indicating disrupted function. Additionally, Sholl analysis revealed reduction branching length both human CLCN4 KD neurons. Finally, along with dendrite abnormalities restored after treatment. These suggest outgrowth synapse remodeling may serve endophenotypic targets for efficacy

Language: Английский

Citations

1
Cognitive outcomes caused by low-level lead, cadmium, and mercury mixture exposure at distinct phases of brain development DOI Creative Commons

Lu Ouyang,

Qi Li,

Shaoqi Rao

et al.

Food and Chemical Toxicology, Journal Year: 2023, Volume and Issue: 175, P. 113707 - 113707

Published: March 7, 2023

Contaminated water and food are the main sources of lead, cadmium, mercury in human body. Long-term low-level ingestion these toxic heavy metals may affect brain development cognition. However, neurotoxic effects exposure to mixture (Pb + Cd Hg) at different stages rarely elucidated. In this study, doses Pb Hg were administered Sprague-Dawley rats via drinking during critical stage development, late stage, after maturation, respectively. Our findings showed that decreased density memory- learning-related dendritic spines hippocampus period resulting hippocampus-dependent spatial memory deficits. Only was reduced phase a higher-dose required, which led hippocampus-independent abnormalities. Exposure maturation revealed no significant change or cognitive function. Further molecular analysis indicated morphological functional changes caused by associated with PSD95 GluA1 dysregulation. Collectively, on cognition varied depending stages.

Language: Английский

Citations

17
Modulation of cholesterol metabolism with Phytoremedies in Alzheimer’s disease: A comprehensive review DOI
Sushruta Koppula, Nitu L. Wankhede, Shivkumar S. Sammeta

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102389 - 102389

Published: June 19, 2024

Language: Английский

Citations

5
Mechanical regulation of synapse formation and plasticity DOI Creative Commons
Takunori Minegishi, Ria Fajarwati Kastian, Naoyuki Inagaki

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 140, P. 82 - 89

Published: June 1, 2022

Dendritic spines are small protrusions arising from dendrites and constitute the major compartment of excitatory post-synapses. They change in number, shape, size throughout life; these changes thought to be associated with formation reorganization neuronal networks underlying learning memory. As brain surrounded by microenvironment including neighboring cells extracellular matrix, their protrusion requires generation force push against structures. In turn, receive protruding spines. Recent studies have identified BAR-domain proteins as being involved membrane deformation initiate spine formation. addition, forces for dendritic filopodium extension activity-induced expansion generated through cooperation between actin polymerization clutch coupling. On other hand, expanding affects neurotransmitter release presynaptic terminals. Here, we review recent advances our understanding physical aspects synapse plasticity, mainly focusing on dynamics.

Language: Английский

Citations

22
Low dose deltamethrin exposure affects gene expression in rat frontal cortex DOI Creative Commons

Junze Wu,

Ankit Shah, Rashika El Ridi

et al.

Translation The University of Toledo Journal of Medical Sciences, Journal Year: 2025, Volume and Issue: 13(S1)

Published: Feb. 5, 2025

Pyrethroids are a class of commonly used synthetic insecticides, widely in agricultural and residential settings due to their efficacy relatively low environmental impact. Nonetheless, epidemiological studies have found that exposure pyrethroids during developmental stages is linked risk for neurodevelopmental disorders. However, the molecular mechanisms behind these neurotoxic effects remain unclear. Our study investigates impact oral deltamethrin, Type II pyrethroid pesticide, on gene expression frontal cortex rats. We differential data from dissections male Long-Evans rats exposed 3 mg/kg dose deltamethrin (or vehicle) perform 3Pod analysis R Studio, which included GSEA, Enrichr, iLINCS analyses. who were had significant changes pathways related inflammation, apoptosis, cellular energy metabolism, synapses. provides important insight pesticide brain possible treatments preventions. This also emphasizes need further research pesticides relationship

Language: Английский

Citations

0
MiR-18a-LncRNA NONRATG-022419 pairs targeted PRG-1 regulates diabetic induced cognitive impairment by regulating NGF\BDNF-Trkb signaling pathway DOI Creative Commons
Qiong Xiang, Hu Lin,

Jia‐Sheng Tao

et al.

Proteome Science, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 6, 2025

Diabetic encephalopathy (DE) is considered as one of the complications diabetes,which associated with cognitive impairment in pathological process development. Up to now, phospholipid phosphatase related 4 (Plppr4), also known plasticity gene 1 (PRG-1) has been revealed its important role neuroplasticity. However, underlying mechanisms Plppr4 on basis diabetic-induced dysfunction (DCD) are still unknown. The aim current study was provide insight into molecular mechanism and cellular heterogeneity DCD, investigate functional PRG-1 involved this process. Combined Single-cell RNA sequencing (scRNA-seq) transcriptome analysis, distinct sub-populations, well potential enriched signaling pathways hippocampal cells could be elucidated. We identified sub-cluster type I spiral ganglion neurons expressed marker Amigo2 cluster8 Cnr1 cluster 9 from DCD effect those neuronal interaction. found that synaptic regulation hippocampus via NGF\BDNF-Trkb pathway. In high glucose induced HT22 injury model vitro, we investigated down-regulated along BDNF decreased expression synapsin-1, PSD-95, SYN which plasticity; Meanwhile, Prg-1 targeted miR-18a-LncRNA NONRATG-022419 pairs significantly PRG-1. This might therapeutic target biomarkers for early interventions patients.

Language: Английский

Citations

0
Habituation to novel stimuli alters hippocampal plasticity associated with morphine tolerance in male Wistar rats DOI

Ghazaleh Ghamkharinejad,

Francesca Mottarlini,

Zohreh Tavassoli

et al.

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149508 - 149508

Published: Feb. 1, 2025

Language: Английский

Citations

0