Mitochondrial SIRT3 Deficiency Results in Neuronal Network Hyperexcitability, Accelerates Age-Related A β Pathology, and Renders Neurons Vulnerable to Aβ Toxicity
AbstractAging is the major risk factor for Alzheimer ’s disease (AD). Mitochondrial dysfunction and neuronal network hyperexcitability are two age-related alterations implicated in AD pathogenesis. We found that levels of the mitochondrial protein deacetylase sirtuin-3 (SIRT3) are significantly reduced, and consequently mitochondria protein acetylat ion is increased in brain cells during aging. SIRT3-deficient mice exhibit robust mitochondrial protein hyperacetylation and reduced mitochondrial mass during aging. Moreover, SIRT3-deficient mice exhibit epileptiform and burst-firing electroencephalogram activity indicating ...
Source: NeuroMolecular Medicine - June 24, 2022 Category: Neurology Source Type: research
Gastrodin Regulates the Notch-1 Signal Pathway via Renin –Angiotensin System in Activated Microglia
This study explored the possible interaction between this two pathways, and to determine whether gastrodin would exert its effects on both of them. Expression of RAS, Notch-1 signaling and proinflammatory mediators in lipopolysaccharide (LPS) activated BV-2 microglia subjected to various treatments was determined by Western blot and immunofluorescence. The protein expression of RAS, Notch-1 pathway and TNF- α and IL-1β was significantly increased in activated microglia. Exogenous Ang II markedly enhanced the expression of these biomarkers. Meanwhile, Azilsartan [a specific inhibitor of AT1 (AT1I)] inhibited the expressio...
Source: NeuroMolecular Medicine - June 24, 2022 Category: Neurology Source Type: research
Mitochondrial SIRT3 Deficiency Results in Neuronal Network Hyperexcitability, Accelerates Age-Related A β Pathology, and Renders Neurons Vulnerable to Aβ Toxicity
AbstractAging is the major risk factor for Alzheimer ’s disease (AD). Mitochondrial dysfunction and neuronal network hyperexcitability are two age-related alterations implicated in AD pathogenesis. We found that levels of the mitochondrial protein deacetylase sirtuin-3 (SIRT3) are significantly reduced, and consequently mitochondria protein acetylat ion is increased in brain cells during aging. SIRT3-deficient mice exhibit robust mitochondrial protein hyperacetylation and reduced mitochondrial mass during aging. Moreover, SIRT3-deficient mice exhibit epileptiform and burst-firing electroencephalogram activity indicating ...
Source: NeuroMolecular Medicine - June 24, 2022 Category: Neurology Source Type: research
Gastrodin Regulates the Notch-1 Signal Pathway via Renin –Angiotensin System in Activated Microglia
This study explored the possible interaction between this two pathways, and to determine whether gastrodin would exert its effects on both of them. Expression of RAS, Notch-1 signaling and proinflammatory mediators in lipopolysaccharide (LPS) activated BV-2 microglia subjected to various treatments was determined by Western blot and immunofluorescence. The protein expression of RAS, Notch-1 pathway and TNF- α and IL-1β was significantly increased in activated microglia. Exogenous Ang II markedly enhanced the expression of these biomarkers. Meanwhile, Azilsartan [a specific inhibitor of AT1 (AT1I)] inhibited the expressio...
Source: NeuroMolecular Medicine - June 24, 2022 Category: Neurology Source Type: research
ZEB1 is a Subgroup-Specific Marker of Prognosis and Potential Drug Target in Medulloblastoma
AbstractMedulloblastoma (MB) is a malignant brain tumor that afflicts mostly children and adolescents and presents four distinct molecular subgroups, known as WNT, SHH, Group 3, and Group 4. ZEB1 is a transcription factor that promotes the expression of mesenchymal markers while restraining expression of epithelial and polarity genes. Because of ZEB1 involvement in cerebellum development, here we investigated the role of ZEB1 in MB. We found increased expression of ZEB1 in MB tumor samples compared to normal cerebellar tissue. Expression was higher in the SHH subgroup when compared to all other MB molecular subgroups. High...
Source: NeuroMolecular Medicine - June 18, 2022 Category: Neurology Source Type: research
Hypercapnia Modulates the Activity of Adenosine A1 Receptors and mitoK+ATP-Channels in Rat Brain When Exposed to Intermittent Hypoxia
This study indicates an increase in the relative number of A1-adenosine receptors in astrocytes and in cells next to the stroke region of the cerebral cortex in rats exposed to hypoxia and hypercapnic hypoxia, but not hypercapnia alone. Hypercapnia and hypoxia increase the relative number of mitoK+ATP-channels in astrocytes and in cells of the peri-infarct region of the cerebral cortex in rats. In an in vitro study, hypercapnia mitigates the effects of acute chemical hypoxia observed in astrocytes for A1-adenosine receptors and mitoK+ATP-channels. Hypercapnia, unlike hypoxia, does not affect the relative number of A1 recep...
Source: NeuroMolecular Medicine - June 1, 2022 Category: Neurology Source Type: research
Influence of Simulated Deep Brain Stimulation on the Expression of Inflammatory Mediators by Human Central Nervous System Cells In Vitro
AbstractDeep brain stimulation (DBS) seems to modulate inflammatory processes. Whether this modulation leads to an induction or suppression of inflammatory mediators is still controversially discussed. Most studies of the influence of electrical stimulation on inflammation were conducted in rodent models with direct current stimulation and/or long impulses, both of which differ from the pattern in DBS. This makes comparisons with the clinical condition difficult. We established an in-vitro model that simulated clinical stimulation patterns to investigate the influence of electrical stimulation on proliferation and survival...
Source: NeuroMolecular Medicine - June 1, 2022 Category: Neurology Source Type: research
Receptor-Interacting Protein 140 Enhanced Temozolomide-Induced Cellular Apoptosis Through Regulation of E2F1 in Human Glioma Cell Lines
This study helps improve our understanding of glioma recurrence and may facilitate the development of more effective treatments. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - June 1, 2022 Category: Neurology Source Type: research
Long Noncoding RNA LINC01518 Modulates Proliferation and Migration in TGF- β1-Treated Human Tenon Capsule Fibroblast Cells Through the Regulation of hsa-miR-216b-5p
In this study, we investigated the expression and functions of long noncoding RNAs (LncRNAs) of LINC01518 in an in vitro model of TGF- β1-treated human Tenon capsule fibroblast (HTF) cells. qRT-PCR was used to examine LINC01518 expression in in situ human glaucoma tissues, and in vitro HTF cells treated with TGF-β1. Lentivirus-mediated LINC01518 knockdown was performed in HTF cells to investigate its effect on TGF-β1-induced cel l proliferation, migration and autophagy signaling pathway. The potential ceRNA candidate of LINC01518, hsa-miR-216b-5p, was probed by dual-luciferase assay and qRT-PCR. Hsa-miR-216b-5p was also...
Source: NeuroMolecular Medicine - June 1, 2022 Category: Neurology Source Type: research
Gastrodin Attenuates Lipopolysaccharide-Induced Inflammatory Response and Migration via the Notch-1 Signaling Pathway in Activated Microglia
AbstractMicroglia-mediated neuroinflammation is known to play a pivotal role in the pathogenesis of different neurological diseases. Gastrodin, a phenolic glucoside, has been reported to exert anti-inflammatory effects in activated microglia challenged with lipopolysaccharide (LPS); however, the underlying mechanism has remained obscure. The present study aimed to ascertain if Gastrodin would regulate the Notch signaling pathway involved in microglia activation. We show here that LPS increased the expression of various members of the Notch-1 pathway, including intracellular Notch receptor domain (NICD), recombining binding...
Source: NeuroMolecular Medicine - June 1, 2022 Category: Neurology Source Type: research
Role of Exosomes in Mediating the Cross-Talk Between Adipose Tissue and the Brain
AbstractAdipose tissue is recognized as the largest endocrine organ by releasing secretory factors to exert systemic function on the brain. Exosomes are one type of extracellular vesicles that transport bioactive molecules between cells and organs. The cargo delivered by exosomes can alter a wide range of cellular responses in recipient cells and play an important pathophysiological role in human diseases. Emerging research showed that adipose tissue-released exosomes could be one of the mechanisms to mediate the function of the brain. Here, we review the modulatory function of adipose tissue-released exosomes in the brain...
Source: NeuroMolecular Medicine - June 1, 2022 Category: Neurology Source Type: research
Neural Stem Cells Secretome Increased Neurogenesis and Behavioral Performance and the Activation of Wnt/ β-Catenin Signaling Pathway in Mouse Model of Alzheimer’s Disease
In this study, mice were randomly allocated into three different groups as follows: Control, AD + Vehicle, and AD + NSCs-CM groups. To induce mouse model of AD, A β1-42 was injected into intracerebroventricular region. Following AD-like confirmation through thioflavin S staining and Passive avoidance test, about 5 µl mouse NSCs-CM was injected into the target areas 21 days after AD induction. For evaluation of endogenous proliferation rate (BrdU/Nestin+ cells), 50 µg/kbW BrdU was intraperitoneally injected for 5 consecutive days. To track NSC differentiation, percent of BrdU/NeuN+ cells were monitored via im...
Source: NeuroMolecular Medicine - May 16, 2022 Category: Neurology Source Type: research
Effect of GNE Mutations on Cytoskeletal Network Proteins: Potential Gateway to Understand Pathomechanism of GNEM
AbstractGNE myopathy is an inherited neuromuscular disorder caused by mutations in GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetyl mannosamine kinase) gene catalyzing the sialic acid biosynthesis pathway. The characteristic features include muscle weakness in upper and lower extremities, skeletal muscle wasting, and rimmed vacuole formation. More than 200 GNE mutations in either epimerase or kinase domain have been reported worldwide. In Indian subcontinent, several GNE mutations have been recently identified with unknown functional correlation. Alternate role of GNE in various cellular processes such as cell adhesion, m...
Source: NeuroMolecular Medicine - May 3, 2022 Category: Neurology Source Type: research
