High Vulnerability of Oligodendrocytes to Oxidative Stress Induced by Ultrafine Urban Particles

Oligodendrocytes, myelin-forming cells in the brain, are vulnerable to oxidative stress. Recent work indicates that air pollution causes demyelinating diseases such as multiple sclerosis. However, little is known about the mechanism of toxicity of ultrafine particulate matters (PMs) to oligodendrocytes. Here, we aimed to determine whether oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs) are more vulnerable to ultrafine urban PMs (uf-UPs) than other types of brain cells and damage to adult OPCs and mOLs in the mouse brain exposed to uf-UPs. For in vitro experiments, following exposure to various concentrations (2, 20, and 200 μg/mL) of uf-UPs, we measured survival rates, the amount of reactive oxygen species (ROS), and the total antioxidant capacities (TACs) of brain cells isolated from neonatal Sprague-Dawley rats. For animal experiments, after a four-week exposure to a uf-UP suspension (20 μL, 0.4 mg/mL), we enumerated the number of damaged cells and typed damaged cells in the white matter of the cerebellum of uf-UP-exposed mice. MTT assays and Hoechst staining demonstrated that OPCs and mOLs were more vulnerable to uf-UP-induced damage than astrocytes and cortical neurons at 2, 20, and 200 μg/mL of uf-UPs examined in this study (p < 0.05). Damage to OPCs and mOLs depended on uf-UP concentration. DCF assays and DHE staining indicated that the amount of ROS generated in OPCs and mOLs was significantly higher than in other brain cell types (p < 0.05). In contrast, TAC values in OPCs and mOLs were significantly lower than those of other brain cell types (p < 0.05). Fluoro-Jade B (FJB)-positive cells in the cerebellar white matter of the uf-UP-exposed group were significantly greater in number relative to the control group. Double immunofluorescence indicated that FJB-positive cells are NG2-positive adult OPCs and carbon anhydrase II-positive mOLs. Taken together, our findings suggest that oxidative stress induced by uf-UPs in the brain impairs adult OPCs and mOLs, causing demyelination and reducing the capacity for remyelination.

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SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium

10.1101/2020.03.31.013268 ◽

2020 ◽

Cited By ~ 31

Author(s):

Leon Fodoulian ◽

Joel Tuberosa ◽

Daniel Rossier ◽

Madlaina Boillat ◽

Chenda Kan ◽

...

Keyword(s):

Sensory System ◽

Cell Types ◽

Sensory Epithelium ◽

Brain Cell ◽

Rna Seq ◽

Angiotensin Converting Enzyme 2 ◽

Sustentacular Cells ◽

The Brain ◽

Brain Cell Types ◽

Human And Mouse

AbstractVarious reports indicate an association between COVID-19 and anosmia, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2), and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. We then observed that the ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.

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Brain Microenvironment Heterogeneity: Potential Value for Brain Tumors

Frontiers in Oncology ◽

10.3389/fonc.2021.714428 ◽

2021 ◽

Vol 11 ◽

Author(s):

Laura Álvaro-Espinosa ◽

Ana de Pablos-Aragoneses ◽

Manuel Valiente ◽

Neibla Priego

Keyword(s):

Brain Tumors ◽

Single Cell ◽

Brain Injuries ◽

Clinical Work ◽

Cell Types ◽

Brain Cell ◽

Brain Disorders ◽

Brain Connectome ◽

The Brain ◽

Brain Cell Types

Uncovering the complexity of the microenvironment that emerges in brain disorders is key to identify potential vulnerabilities that might help challenging diseases affecting this organ. Recently, genomic and proteomic analyses, especially at the single cell level, have reported previously unrecognized diversity within brain cell types. The complexity of the brain microenvironment increases during disease partly due to the immune infiltration from the periphery that contributes to redefine the brain connectome by establishing a new crosstalk with resident brain cell types. Within the rewired brain ecosystem, glial cell subpopulations are emerging hubs modulating the dialogue between the Immune System and the Central Nervous System with important consequences in the progression of brain tumors and other disorders. Single cell technologies are crucial not only to define and track the origin of disease-associated cell types, but also to identify their molecular similarities and differences that might be linked to specific brain injuries. These altered molecular patterns derived from reprogramming the healthy brain into an injured organ, might provide a new generation of therapeutic targets to challenge highly prevalent and lethal brain disorders that remain incurable with unprecedented specificity and limited toxicities. In this perspective, we present the most relevant clinical and pre-clinical work regarding the characterization of the heterogeneity within different components of the microenvironment in the healthy and injured brain with a special interest on single cell analysis. Finally, we discuss how understanding the diversity of the brain microenvironment could be exploited for translational purposes, particularly in primary and secondary tumors affecting the brain.

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Resistance of nerve cells to oxidative injury

Medicinski pregled ◽

10.2298/mpns1108386j ◽

2011 ◽

Vol 64 (7-8) ◽

pp. 386-391 ◽

Cited By ~ 3

Author(s):

Zorica Jovanovic ◽

Svetlana Jovanovic

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Hydrogen Peroxide ◽

Neuronal Damage ◽

Reactive Oxygen ◽

Cell Types ◽

Brain Cell ◽

Nerve Cells ◽

Oxygen Species ◽

The Brain

Introduction. Reactive oxygen species are particularly active in the brain and neuronal tissue, and they are involved in numerous cellular functions, including cell death and survival. Brain and oxidative stress. A high metabolic rate and an abundant supply of the transition metals make the brain an ideal target for a free radical attack. In addition, the brain has a high susceptibility to oxidative stress due to the high lipid content and relatively lower regenerative capacity in comparison with other tissues. Vulnerability of nerve cells to oxidative stress. The neurons are more vulnerable to oxidative stress than other brain cell types. In addition to the two conventional enzymes, catalase and glutathione peroxidase, peroxiredoxins remove intracellular hydrogen peroxide by reducing it to water. The recent work increasingly supports the hypothesis that peroxiredoxins are not only antioxidant proteins, but they also play a role in cell signaling by controlling hydrogen peroxide and alkyl hydroperoxide levels. The accumulating evidence demonstrates that microglia can become deleterious and damage neurons. The overactivated microglia release reactive oxygen species that cause neuronal damage in neurodegenerative diseases. Conclusion. The defense of nerve cells against reactive oxygen species - mediated oxidative damage is essential for maintaining the functionality of nerve cells. The ongoing studies show that neuron-glial compartmentalization of antioxidants is critical for the neuronal signaling by hydrogen peroxide as well as the neuronal protection.

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Establishment and Preliminary Characterization of Three Astrocytic Cells Lines Obtained from Primary Rat Astrocytes by Sub-Cloning

Genes ◽

10.3390/genes11121502 ◽

2020 ◽

Vol 11 (12) ◽

pp. 1502

Author(s):

Fabio Caradonna ◽

Gabriella Schiera ◽

Carlo Maria Di Liegro ◽

Vincenzo Vitale ◽

Ilenia Cruciata ◽

...

Keyword(s):

Cell Lines ◽

Cell Types ◽

Brain Parenchyma ◽

Brain Cell ◽

The Other ◽

Cellular Events ◽

Rat Astrocytes ◽

The Brain ◽

Brain Cell Types

Gliomas are complex and heterogeneous tumors that originate from the glial cells of the brain. The malignant cells undergo deep modifications of their metabolism, and acquire the capacity to invade the brain parenchyma and to induce epigenetic modifications in the other brain cell types. In spite of the efforts made to define the pathology at the molecular level, and to set novel approaches to reach the infiltrating cells, gliomas are still fatal. In order to gain a better knowledge of the cellular events that accompany astrocyte transformation, we developed three increasingly transformed astrocyte cell lines, starting from primary rat cortical astrocytes, and analyzed them at the cytogenetic and epigenetic level. In parallel, we also studied the expression of the differentiation-related H1.0 linker histone variant to evaluate its possible modification in relation with transformation. We found that the most modified astrocytes (A-FC6) have epigenetic and chromosomal alterations typical of cancer, and that the other two clones (A-GS1 and A-VV5) have intermediate properties. Surprisingly, the differentiation-specific somatic histone H1.0 steadily increases from the normal astrocytes to the most transformed ones. As a whole, our results suggest that these three cell lines, together with the starting primary cells, constitute a potential model for studying glioma development.

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Genetic identification Of brain cell types underlying schizophrenia

10.1101/145466 ◽

2017 ◽

Cited By ~ 10

Author(s):

Nathan G. Skene ◽

Julien Bryois ◽

Trygve E. Bakken ◽

Gerome Breen ◽

James J Crowley ◽

...

Keyword(s):

Pyramidal Cells ◽

Cell Types ◽

Brain Cell ◽

Common Variant ◽

Genetic Identification ◽

Medium Spiny Neurons ◽

Gene Sets ◽

The Common ◽

The Brain ◽

Brain Cell Types

AbstractWith few exceptions, the marked advances in knowledge about the genetic basis for schizophrenia have not converged on findings that can be confidently used for precise experimental modeling. Applying knowledge of the cellular taxonomy of the brain from single-cell RNA-sequencing, we evaluated whether the genomic loci implicated in schizophrenia map onto specific brain cell types. The common variant genomic results consistently mapped to pyramidal cells, medium spiny neurons, and certain interneurons but far less consistently to embryonic, progenitor, or glial cells. These enrichments were due to distinct sets of genes specifically expressed in each of these cell types. Many of the diverse gene sets associated with schizophrenia (including antipsychotic targets) implicate the same brain cell types. Our results provide a parsimonious explanation: the common-variant genetic results for schizophrenia point at a limited set of neurons, and the gene sets point to the same cells. While some of the genetic risk is associated with GABAergic interneurons, this risk largely does not overlap with that from projecting cells.

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Paraoxonase-1 and -3 Protein Expression in the Brain of the Tg2576 Mouse Model of Alzheimer’s Disease

Antioxidants ◽

10.3390/antiox10030339 ◽

2021 ◽

Vol 10 (3) ◽

pp. 339

Author(s):

Jose Gregorio Salazar ◽

Judit Marsillach ◽

Ingrid Reverte ◽

Bharti Mackness ◽

Michael Mackness ◽

...

Keyword(s):

Mouse Model ◽

Protein Expression ◽

Neurodegenerative Diseases ◽

Cell Types ◽

Brain Regions ◽

Brain Cell ◽

Paraoxonase 1 ◽

Tg2576 Mouse ◽

The Brain ◽

Brain Cell Types

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and -3 (PON1 and PON3) protein expression was demonstrated in tissue with no PON1 or PON3 gene expression. In the present study, we examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Methods: we used peroxidase- and fluorescence-based immunohistochemistry in five brain regions (olfactory bulb, forebrain, posterior midbrain, hindbrain and cerebellum) of transgenic (Tg2576) mice with the Swedish mutation (KM670/671NL) responsible for a familial form of AD and corresponding wild-type mice. Results: We found intense PON1 and PON3-positive staining in star-shaped cells surrounding Aβ plaques in all the studied Tg2576 mouse-brain regions. Although we could not colocalize PON1 and PON3 with astrocytes (star-shaped cells in the brain), we found some PON3 colocalization with microglia. Conclusions: These results suggest that (1) PON1 and PON3 cross the blood–brain barrier in discoidal high-density lipoproteins (HDLs) and are transferred to specific brain-cell types; and (2) PON1 and PON3 play an important role in preventing oxidative stress and lipid peroxidation in particular brain-cell types (likely to be glial cells) in AD pathology and potentially in other neurodegenerative diseases as well.

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High-fat diet-induced obesity and impairment of brain neurotransmitter pool

Translational Neuroscience ◽

10.1515/tnsci-2020-0099 ◽

2020 ◽

Vol 11 (1) ◽

pp. 147-160

Author(s):

Ranyah Shaker M. Labban ◽

Hanan Alfawaz ◽

Ahmed T. Almnaizel ◽

Wail M. Hassan ◽

Ramesa Shafi Bhat ◽

...

Keyword(s):

Oxidative Stress ◽

Brain Tissue ◽

High Fat Diet ◽

Density Lipoprotein ◽

Obese Group ◽

Control Group ◽

High Fat ◽

Brain Neurotransmitter ◽

The Brain ◽

Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

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Effect of Water and Ethanol Extracts from Hericium erinaceus Solid-State Fermented Wheat Product on the Protection and Repair of Brain Cells in Zebrafish Embryos

Molecules ◽

10.3390/molecules26113297 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3297

Author(s):

Shun-Kuo Sun ◽

Chun-Yi Ho ◽

Wei-Yang Yen ◽

Su-Der Chen

Keyword(s):

Solid State ◽

Brain Cell ◽

Hot Water ◽

Raw Material ◽

Brain Cells ◽

Zebrafish Embryos ◽

Hericium Erinaceus ◽

Water Extracts ◽

The Brain ◽

Wheat Product

Extracts from Hericium erinaceus can cause neural cells to produce nerve growth factor (NGF) and protect against neuron death. The objective of this study was to evaluate the effects of ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product on the brain cells of zebrafish embryos in both pre-dosing protection mode and post-dosing repair mode. The results showed that 1% ethanol could effectively promote zebrafish embryo brain cell death. Both 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product protected brain cells and significantly reduced the death of brain cells caused by 1% ethanol treatment in zebrafish. Moreover, the zebrafish embryos were immersed in 1% ethanol for 4 h to cause brain cell damage and were then transferred and soaked in the 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product to restore the brain cells damaged by the 1% ethanol. However, the 200 ppm extracts from the unfermented wheat medium had no protective and repairing effects. Moreover, 200 ppm of ethanol and water extracts from H. erinaceus fruiting body had less significant protective and restorative effects on the brain cells of zebrafish embryos. Both the ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product could protect and repair the brain cells of zebrafish embryos damaged by 1% ethanol. Therefore, it has great potential as a raw material for neuroprotective health product.

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Effect of elevated potassium on the ion content of mouse astrocytes and neurons

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-271 ◽

1992 ◽

Vol 70 (S1) ◽

pp. S263-S268 ◽

Cited By ~ 23

Author(s):

H. Steve White ◽

Sien Yao Chow ◽

Y. C. Yen-Chow ◽

Dixon M. Woodbury

Keyword(s):

Cortical Neurons ◽

Cell Types ◽

Mouse Cell ◽

Ion Concentration ◽

Cellular Heterogeneity ◽

Resting Membrane Potential ◽

Extracellular Potassium ◽

Individual Response ◽

Extracellular Potassium Concentration ◽

The Brain

Potassium is tightly regulated within the extracellular compartment of the brain. Nonetheless, it can increase 3- to 4-fold during periods of intense seizure activity and 10- to 20-fold under certain pathological conditions such as spreading depression. Within the central nervous system, neurons and astrocytes are both affected by shifts in the extracellular concentration of potassium. Elevated potassium can lead to a redistribution of other ions (e.g., calcium, sodium, chloride, hydrogen, etc.) within the cellular compartment of the brain. Small shifts in the extracellular potassium concentration can markedly affect acid–base homeostasis, energy metabolism, and volume regulation of these two brain cells. Since normal neuronal function is tightly coupled to the ability of the surrounding glial cells to regulate ionic shifts within the brain and since both cell types can be affected by shifts in the extracellular potassium, it is important to characterize their individual response to an elevation of this ion. This review describes the results of side-by-side studies conducted on cortical neurons and astrocytes, which assessed the effect of elevated potassium on their resting membrane potential, intracellular volume, and their intracellular concentration of potassium, sodium, and chloride. The results obtained from these studies suggest that there exists a marked cellular heterogeneity between neurons and astrocytes in their response to an elevation in the extracellular potassium concentration.Key words: astrocytes, neurons, ion concentration, neuronal–glial interactions, mouse, cell culture.

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The Effect of Herniarin on Spatial Working Memory, Pain Threshold, and Oxidative Stress in Ischemic Hypoperfusion Model in Rats

Caspian Journal of Neurological Sciences ◽

10.32598/cjns.7.24.5 ◽

2021 ◽

Vol 7 (1) ◽

pp. 42-50

Author(s):

Zahra Nazari Barchestani ◽

◽

Maryam Rafieirad ◽

Keyword(s):

Oxidative Stress ◽

Pain Threshold ◽

Male Rats ◽

Control Group ◽

Tail Flick ◽

Pain Thresholds ◽

Ischemic Group ◽

Significant Difference ◽

The Brain ◽

And Oxidative Stress

Background: Ischemia causes severe neuronal damage and induces oxidative stress, memory impairment, and reduces pain threshold. Herniarin is a powerful antioxidant. Objectives: This study aimed to evaluate the effect of herniarin on memory, pain, and oxidative stress in an ischemia model in male rats. Materials & Methods: In this study, 50 male rats were divided into 5 groups of control, sham, ischemic, and two other ischemic groups, which received herniarin at doses of 150 and 300 mg/kg by gavage for 14 days. Behavioral tests were performed by shuttle box, and Y-maze and pain tests were performed by Tail-Flick test. Then, the rats’ brains were extracted to evaluate lipid peroxidation and measure the levels of thiol and Glutathione Peroxidase (GPX) in the hippocampus and striatum tissues. The results were expressed as Mean±SEM and then analyzed using suitable statistical methods of ANOVA and least significant difference post-hoc test in SPSS V. 20. Results: Herniarin significantly increased the avoidance memory, spatial memory, and pain thresholds of ischemic rats at different concentrations (P<0.001). Besides, the amount of malondialdehyde (MDA) and thiol in the ischemic group increased significantly in comparison to the control group (P<0.001). Also, in the ischemic group, GPX (P<0.001) significantly decreased. Decreased MDA (P<0.001) and thiol (P<0.001) and increased GPX levels were observed with herniarin administration (P<0.01). Conclusion: According to this study’s results, herniarin can remove free radicals and oxidant substances from the brain. Thus, it improves memory and pain thresholds in the brain hypoperfusion ischemia model.

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