Roles of Neuronal Protein Kinase C ε on Endoplasmic Reticulum Stress and Autophagic Formation in Diabetic Neuropathy
AbstractIn chronic diabetic neuropathy (DN), the cellular mechanisms of neuropathic pain remain unclear. Protein kinase C epsilon (PKC ε) is an intracellular signaling molecule that mediates chronic pain. This paper addresses the long-term upregulated PKCε in DN associated with endoplasmic reticulum (ER) stress and autophagic formation and correlates to chronic neuropathic pain. We found that thermal hyperalgesia and mechanical a llodynia course development were associated with PKCε upregulation after DN but not skin denervation. Pathologically, PKCε upregulation was associated with the expression of inositol-requiring...
Source: Molecular Neurobiology - April 25, 2024 Category: Neurology Source Type: research
Association between Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4) Locus and Early-Onset Anti-acetylcholine Receptor-Positive Myasthenia Gravis in Serbian Patients
AbstractGenome-wide association studies (GWAS) have provided strong evidence that early- and late-onset MG have different genetic backgrounds. Recent in silico analysis based on GWAS results revealed rs231735 and rs231770 variants withinCTLA-4 locus as possible MG causative genetic factors. We aimed to explore the association of rs231735 and rs231770 with MG in a representative cohort of Serbian patients. We conducted an age-, sex-, and ethnicity-matched case –control study. Using TaqMan allele discrimination assays, the frequency of rs231735 and rs231770 genetic variants was examined in 447 AChR-MG patients and 447 matc...
Source: Molecular Neurobiology - April 23, 2024 Category: Neurology Source Type: research
Neuronal Mitochondrial Calcium Uniporter (MCU) Deficiency Is Neuroprotective in Hyperexcitability by Modulation of Metabolic Pathways and ROS Balance
This study highlights the importance of MCU at the interface of Ca2+ handling and metabolism as a mediator of stress-related mitochondrial dysfunction, which indicates the modulation of MCU as a potential target for future antiepileptogenic therapy. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - April 23, 2024 Category: Neurology Source Type: research
Purinergic Signalling Mediates Aberrant Excitability of Developing Neuronal Circuits in the Fmr1 Knockout Mouse Model
In this study, we examined whether elevated astrocyte purinergic signalling also impacts neuronal morphology and connectivity ofFmr1 KO cortical neurons. Here, we found that conditioned media from primaryFmr1 KO astrocytes was sufficient to enhance neurite extension and complexity of both wildtype andFmr1 KO neurons to a similar degree as UTP-mediated outgrowth. Significantly enhanced firing was also observed inFmr1 KO neuron-astrocyte co-cultures grown on microelectrode arrays but was associated with large deficits in firing synchrony. The selective P2Y2 purinergic receptor antagonist AR-C 118925XX effectively normalized ...
Source: Molecular Neurobiology - April 23, 2024 Category: Neurology Source Type: research
Correction: m6A-Induced lncRNA MEG3 Promotes Cerebral Ischemia-Reperfusion Injury Via Modulating Oxidative Stress and Mitochondrial Dysfunction by hnRNPA1/Sirt2 Axis
(Source: Molecular Neurobiology)
Source: Molecular Neurobiology - April 23, 2024 Category: Neurology Source Type: research
Bioinformatics Approach to Identify the Pathogenetic Link of Gut Microbiota-Derived Short-Chain Fatty Acids and Ischemic Stroke
In conclusion, this paper analyzes the involvement of SCFAs in the complex gut-brain axis mechanism, which contributes to developing new targets for treating central nervous system diseases and provides new ideas for early ischemic stroke diagnosis. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - April 22, 2024 Category: Neurology Source Type: research
Ultra-Low-Dose UV-C Photo-stimulation Promotes Neural Stem Cells Differentiation via Presenilin 1 Mediated Notch and β-Catenin Activation
In this study, we focused on utilizing ultraviolet-C (UV-C) at a specific wavelength of 254 nm, with an ultra-low dose at intensity of 330 μW/cm2 and a total energy of 594 mJ/cm2 per day over a period of seven days, to stimulate the proliferation and differentiation of mouse neural stem cells (NSCs). The results revealed that the application of ultra-low-dose UV-C yielded the most significant effect in promoting differentiation when compared to mixed ultraviolet (UV) and ultraviolet-A (UV-A) radiation at equivalent exposure levels. The mechanism exploration elucidated the role of Presenilin 1 in mediating the activat...
Source: Molecular Neurobiology - April 22, 2024 Category: Neurology Source Type: research
TRIM28 Fosters Microglia Ferroptosis via Autophagy Modulation to Enhance Neuropathic Pain and Neuroinflammation
This study explores the molecular underpinnings of neuropathic pain (NPP) and neuroinflammation, focusing on the role of TRIM28 in the regulation of autophagy and microglia ferroptosis. Leveraging transcriptomic data associated with NPP, we identified TRIM28 as a critical regulator of ferroptosis. Through comprehensive analysis, including Gene Ontology enrichment and protein-protein interaction network assessments, we unveiled GSK3B as a downstream target of TRIM28. Experimental validation confirmed the capacity of TRIM28 to suppress GSK3B expression and attenuate autophagic processes in microglia. We probed the consequenc...
Source: Molecular Neurobiology - April 22, 2024 Category: Neurology Source Type: research
Dose-Ranging Effects of the Intracerebral Administration of Atsttrin in Experimental Model of Parkinson ’s Disease Induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Mice
AbstractParkinson ’s disease is one of the most common neurodegenerative disorders characterized by a multitude of motor and non-motor clinical symptoms resulting from the progressive and long-lasting abnormal loss of nigrostriatal dopaminergic neurons. Currently, the available treatments for patients with Parkinso n’s disease are limited and exert only symptomatic effects, without adequate signs of delaying or stopping the progression of the disease. Atsttrin constitutes the bioengineered protein which ultrastructure is based on the polypeptide chain frame of the progranulin (PGRN), which exerts anti-inflam matory eff...
Source: Molecular Neurobiology - April 20, 2024 Category: Neurology Source Type: research
Application of CRISPR/Cas9 System in the Treatment of Alzheimer ’s Disease and Neurodegenerative Diseases
AbstractAlzheimer ’s, Parkinson’s, and Huntington’s are some of the most common neurological disorders, which affect millions of people worldwide. Although there have been many treatments for these diseases, there are still no effective treatments to treat or completely stop these disorders. Perhaps the lack of proper treatment for these diseases can be related to various reasons, but the poor results related to recent clinical research also prompted doctors to look for new treatment approaches. In this regard, various researchers from all over the world have provided many new treatments, one of which is CRISPR/Cas9....
Source: Molecular Neurobiology - April 19, 2024 Category: Neurology Source Type: research
NFATc4 Knockout Promotes Neuroprotection and Retinal Ganglion Cell Regeneration After Optic Nerve Injury
In this study, we investigated the role of the family of transcription factors known as nuclear factor of activated T cells (NFAT), which are expressed in the retina; however, their role in RGC survival after injury is unknown. Using the optic nerve crush (ONC) model, widely employed to study optic neuropathies and central nervous system axon injury, we found that NFATc4 is specifically but transiently up-regulated in response to mechanical injury. In the injured retina, NFATc4 immunolocalized primarily to the ganglionic cell layer. Utilizing NFATc4−/− and NFATc3−/− mice, we demonstrated that NFATc4, but not NFATc3...
Source: Molecular Neurobiology - April 19, 2024 Category: Neurology Source Type: research
Pharmacological Evidence of Eugenia Brasiliensis Leaves in a Reserpine-Induced Fibromyalgia Model: Antinociceptive, Emotional, Anti-Inflammatory, and Neurotrophic Effects
AbstractFibromyalgia (FM) is a painful chronic condition that significantly impacts the quality of life, posing challenges for clinical management. Given the difficulty of understanding the pathophysiology and finding new therapeutics, this study explored the effects of a medicinal plant,E. brasiliensis, in an FM model induced by reserpine in Swiss mice. Animals were treated with saline 0.9% (vehicle), duloxetine 10 mg/kg (positive control), or hydroalcoholic extract ofE. brasiliensis leaves 300 mg/kg (HEEb). Nociceptive parameters, as well as locomotion, motor coordination, strength, anxiety, and depressive-like behaviors...
Source: Molecular Neurobiology - April 19, 2024 Category: Neurology Source Type: research
Research Hotspots and Frontiers of Alzheimer ’s Disease and Gut Microbiota: A Knowledge Mapping and Text Mining Analysis
This study aimed to conduct a bibliometric and visual analysis of published studies related to gut microbiota and AD. Based on the Web of Science Core Collection SCI-Expanded database, we utilize Excel 2019 and v isualization analysis tools VOSviewer, Co-Occurrence13.2 (COOC13.2), Citespace, HistCite, and Bibliometrix (R-Tool of R-Studio) for analysis. A total of 1093 related kinds of literature were included, and the number of papers presented an overall increasing trend. The country/region with the most p ublications is China, the institution is Zhejiang University, the author is Walter J Lukiw from the USA, and the jo...
Source: Molecular Neurobiology - April 18, 2024 Category: Neurology Source Type: research
Bisphenol-F and Bisphenol-S (BPF and BPS) Impair the Stemness of Neural Stem Cells and Neuronal Fate Decision in the Hippocampus Leading to Cognitive Dysfunctions
AbstractNeurogenesis occurs throughout life in the hippocampus of the brain, and many environmental toxicants inhibit neural stem cell (NSC) function and neuronal generation. Bisphenol-A (BPA), an endocrine disrupter used for surface coating of plastic products causes injury in the developing and adult brain; thus, many countries have banned its usage in plastic consumer products. BPA analogs/alternatives such as bisphenol-F (BPF) and bisphenol-S (BPS) may also cause neurotoxicity; however, their effects on neurogenesis are still not known. We studied the effects of BPF and BPS exposure from gestational day 6 to postnatal ...
Source: Molecular Neurobiology - April 18, 2024 Category: Neurology Source Type: research
Transactivator of Transcription (Tat)-Induced Neuroinflammation as a Key Pathway in Neuronal Dysfunction: A Scoping Review
AbstractThe activity of HIV-1 and its viral proteins within the central nervous system (CNS) is responsible for a wide array of neuropathological effects, resulting in a spectrum of neurocognitive deficits defined as HIV-associated neurocognitive disorders (HAND). Amongst the various viral proteins, the transactivator of transcription (Tat) remains detectable even with effective antiretroviral therapy (ART) and suppressed viremia, highlighting the significance of this protein in the modern ART era. Tat has been extensively researched in both fundamental and clinical settings due to its role in neuroinflammation, neuronal d...
Source: Molecular Neurobiology - April 17, 2024 Category: Neurology Source Type: research
