scholarly journals Conditional Loss of BAF (mSWI/SNF) Scaffolding Subunits Affects Specification and Proliferation of Oligodendrocyte Precursors in Developing Mouse Forebrain

2021 ◽  
Vol 9 ◽  
Author(s):  
Eman Abbas ◽  
Mohamed A. Hassan ◽  
Godwin Sokpor ◽  
Kamila Kiszka ◽  
Linh Pham ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Neural Development ◽  
Conditional Knockout ◽  
Baf Complex ◽  
Ventral Telencephalon ◽  
Mouse Mutants ◽  
Oligodendrocyte Precursor ◽  
Brain And Spinal Cord ◽  
The Brain

Oligodendrocytes are responsible for axon myelination in the brain and spinal cord. Generation of oligodendrocytes entails highly regulated multistage neurodevelopmental events, including proliferation, differentiation and maturation. The chromatin remodeling BAF (mSWI/SNF) complex is a notable regulator of neural development. In our previous studies, we determined the indispensability of the BAF complex scaffolding subunits BAF155 and BAF170 for neurogenesis, whereas their role in gliogenesis is unknown. Here, we show that the expression of BAF155 and BAF170 is essential for the genesis of oligodendrocytes during brain development. We report that the ablation of BAF155 and BAF170 in the dorsal telencephalic (dTel) neural progenitors or in oligodendrocyte-producing progenitors in the ventral telencephalon (vTel) in double-conditional knockout (dcKO) mouse mutants, perturbed the process of oligodendrogenesis. Molecular marker and cell cycle analyses revealed impairment of oligodendrocyte precursor specification and proliferation, as well as overt depletion of oligodendrocytes pool in dcKO mutants. Our findings unveil a central role of BAF155 and BAF170 in oligodendrogenesis, and thus substantiate the involvement of the BAF complex in the production of oligodendrocytes in the forebrain.

scholarly journals Single-cell Sequencing Reveals Brain/Spinal Cord Oligodendrocyte Precursor Heterogeneity and Requirement for mTOR in Cholesterol Biosynthesis and Myelin Maintenance

2020 ◽  
Author(s):  
Luipa Khandker ◽  
Marisa A. Jeffries ◽  
Yun-Juan Chang ◽  
Marie L. Mather ◽  
Jennifer N. Bourne ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Cholesterol Biosynthesis ◽  
Adult Brain ◽  
Cell Analysis ◽  
Sequencing Studies ◽  
Oligodendrocyte Precursor ◽  
Brain And Spinal Cord ◽  
The Brain

AbstractBrain and spinal cord oligodendroglia have distinct functional characteristics, and cell autonomous loss of individual genes can result in different regional phenotypes. However, sequencing studies to date have not revealed distinctions between brain and spinal cord oligodendroglia. Using single-cell analysis of oligodendroglia during myelination, we demonstrate that brain and spinal cord precursors are transcriptionally distinct, defined predominantly by cholesterol biosynthesis. We further identify mechanistic target of rapamycin (mTOR) as a major regulator promoting cholesterol biosynthesis in oligodendroglia. Oligodendroglial-specific loss of mTOR compromises cholesterol biosynthesis in both the brain and spinal cord. Importantly, mTOR loss has a greater impact on cholesterol biosynthesis in spinal cord oligodendroglia that corresponds with more pronounced developmental deficits. However, loss of mTOR in brain oligodendroglia ultimately results in oligodendrocyte death, spontaneous demyelination, and impaired axonal function, demonstrating that mTOR is required for myelin maintenance in the adult brain.

scholarly journals Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids, with Cranial and Caudal Extension

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Mahmood Mubasher ◽  
Aseel Sukik ◽  
Ahmed Hassan El Beltagi ◽  
Ali Rahil
Keyword(s):  
Spinal Cord ◽  
Lower Limbs ◽  
High Dose ◽  
Oral Corticosteroids ◽  
Dose Oral ◽  
Multiple Levels ◽  
Romberg Test ◽  
Brain And Spinal Cord ◽  
The Brain

A 23-year-old lady presented with vertigo and imbalance in walking, blurring of vision, diplopia, and headache, in addition to numbness in the lower limbs over a period of six days. On examination patient had nystagmus, ataxia, positive Romberg test, and hyperreflexia. MRI examination of the brain and spinal cord showed evidence of faint bright signal intensity foci in T2/FLAIR involving bilateral cerebral hemispheres, subcortical deep white matter, bilateral thalami, posterior pons and left brachium pontis, and basal ganglia, with small nodular enhancement that aligned along curvilinear structures; those lesions also were apparent along the spinal cord at multiple levels. The clinical and radiological features suggested CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) syndrome. Symptoms improved dramatically with high dose oral corticosteroids. Our report addresses the radiological and clinical pattern of a case of CLIPPERS rhombencephalitis, with added superior and inferior extension to involve the brain and spinal cord, which is to emphasize the importance of raising the awareness of this disease and the combined role of radiologist and physicians for the diagnosis of this potentially treatable entity, responsive to glucocorticosteroid immunosuppression.

scholarly journals Death Receptors in the Selective Degeneration of Motoneurons in Amyotrophic Lateral Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Julianne Aebischer ◽  
Nathalie Bernard-Marissal ◽  
Brigitte Pettmann ◽  
Cédric Raoul
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Immune Cells ◽  
Microglial Activation ◽  
Death Receptors ◽  
Strong Body ◽  
Als Patients ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

While studies on death receptors have long been restricted to immune cells, the last decade has provided a strong body of evidence for their implication in neuronal death and hence neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). ALS is a fatal paralytic disorder that primarily affects motoneurons in the brain and spinal cord. A neuroinflammatory process, associated with astrocyte and microglial activation as well as infiltration of immune cells, accompanies motoneuron degeneration and supports the contribution of non-cell-autonomous mechanisms in the disease. Hallmarks of Fas, TNFR, LT-βR, and p75NTR signaling have been observed in both animal models and ALS patients. This review summarizes to date knowledge of the role of death receptors in ALS and the link existing between the selective loss of motoneurons and neuroinflammation. It further suggests how this recent evidence could be included in an ultimate multiapproach to treat patients.

61 UNVEILING THE ROLE OF LIPIDS IN ORGANOGESIS: MOLECULAR ANATOMY BY DESORPTION ELECTROSPRAY IONIZATION MASS SPECTROMETRY IMAGING MASS SPECTROMETRY

2016 ◽  
Vol 28 (2) ◽  
pp. 160
Author(s):  
V. Pirro ◽  
P. O. Favaron ◽  
C. R. Ferreira ◽  
L. S. Eberlin ◽  
R. S. Barreto ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Spinal Cord ◽  
Desorption Electrospray Ionization ◽  
Ionization Mass ◽  
Differential Distribution ◽  
Desi Ms ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Digestive Glands

Even though the role of lipids in pandemic diseases such as obesity and diabetes is a focus of increasing research, the role of lipids during organogenesis, when diverse diseases may be triggered, is unexplored. Also, pig embryonic tissues represent an attractive option for organ transplantation. This study introduces a detailed morphological analysis of swine fetal tissues with matching location of lipids acquired by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for the study of differential distribution of free fatty acids (FFA) and phospholipids (PL) in specific organs during fetal development. Samples from a pig fetuses around Day 50 of pregnancy were sectioned at a cryotome and mounted onto glass slides. Fixative agents were not used. DESI-MS images were run with a step size of 300 µm using a morphologically friendly (non-destructive) solvent combination, namely dimethylformamide/acetonitrile 1 : 1 (v/v). Data were acquired in the negative ion mode in the m/z range of 150 to 1000 from different sections representing the whole swine fetus body. Ion images were constructed using BioMAP software. After imaging, the whole-body tissue samples were stained with hematoxylin and eosin (H&E) and were overlaid to the DESI-MS lipid images. Differential distribution of FFA, phosphatidylcholines (PC), phosphatidylserines (PS), sulphatides (ST), and phosphatidylinositols (PI) was observed among organs, especially on nervous and circulatory systems, and digestive glands. Most lipids concentrated in the brain, spinal cord, and digestive glands such as the liver. For example, arachidonic acid was most abundant in neuronal tissue, whereas docosahexaenoic acid predominated in the liver and digestive glands. Distribution of PS (36 : 1) of m/z 788 was observed in all tissues except for the digestive system, but PS (40 : 6) of m/z 834.7 was exclusive of brain and spinal cord. Lipids related to brain and spinal cord were mostly polyunsaturated fatty acids as well as specific PS lipids. Arachidonic and eicosatrienoic acids are more concentrated in hindbrain and spinal cord, whereas PS was more abundant in the brain than in the spinal cord. There is no information on PS chemical composition during brain and spinal cord development, but PS concentration in the nervous tissue membranes varies with age, brain areas, cell type, and subcellular components. Several reports indicate that alteration in PS synthesis might participate in the mechanism of brain damage. Also, PS has been found to be altered in brain tumours. Oleic acid, fatty acid dimers, and the signalling lipid PI (38 : 3) were most significant for the digestive system and liver. Liver is one of the main organs involved in fatty acid metabolism (besides adipose tissue and muscle). By overlying morphological and molecular information, lipids seem to be a major player in the organogenesis process.

scholarly journals EWS–FLI1 modulated alternative splicing of ARID1A reveals novel oncogenic function through the BAF complex

2019 ◽  
Author(s):  
Saravana P Selvanathan ◽  
Garrett T Graham ◽  
Alexander R Grego ◽  
Tabari M Baker ◽  
J Robert Hogg ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Tumor Suppressors ◽  
Drug Targeting ◽  
Mrna Isoforms ◽  
Protein Variant ◽  
Baf Complex ◽  
Oncogenic Driver ◽  
Precise Role ◽  
Oncogenic Function

Abstract Connections between epigenetic reprogramming and transcription or splicing create novel mechanistic networks that can be targeted with tailored therapies. Multiple subunits of the chromatin remodeling BAF complex, including ARID1A, play a role in oncogenesis, either as tumor suppressors or oncogenes. Recent work demonstrated that EWS–FLI1, the oncogenic driver of Ewing sarcoma (ES), plays a role in chromatin regulation through interactions with the BAF complex. However, the specific BAF subunits that interact with EWS–FLI1 and the precise role of the BAF complex in ES oncogenesis remain unknown. In addition to regulating transcription, EWS–FLI1 also alters the splicing of many mRNA isoforms, but the role of splicing modulation in ES oncogenesis is not well understood. We have identified a direct connection between the EWS–FLI1 protein and ARID1A isoform protein variant ARID1A-L. We demonstrate here that ARID1A-L is critical for ES maintenance and supports oncogenic transformation. We further report a novel feed-forward cycle in which EWS–FLI1 leads to preferential splicing of ARID1A-L, promoting ES growth, and ARID1A-L reciprocally promotes EWS–FLI1 protein stability. Dissecting this interaction may lead to improved cancer-specific drug targeting.

scholarly journals MRI in the assessment and monitoring of multiple sclerosis: an update on best practice

2017 ◽  
Vol 10 (6) ◽  
pp. 247-261 ◽  
Author(s):  
Ulrike W. Kaunzner ◽  
Susan A. Gauthier
Keyword(s):  
Multiple Sclerosis ◽  
Best Practice ◽  
High Sensitivity ◽  
The Past ◽  
Assessment And Monitoring ◽  
Magnetic Resonance Imaging Mri ◽  
Improved Technology ◽  
Brain And Spinal Cord ◽  
The Brain

Magnetic resonance imaging (MRI) has developed into the most important tool for the diagnosis and monitoring of multiple sclerosis (MS). Its high sensitivity for the evaluation of inflammatory and neurodegenerative processes in the brain and spinal cord has made it the most commonly used technique for the evaluation of patients with MS. Moreover, MRI has become a powerful tool for treatment monitoring, safety assessment as well as for the prognostication of disease progression. Clinically, the use of MRI has increased in the past couple decades as a result of improved technology and increased availability that now extends well beyond academic centers. Consequently, there are numerous studies supporting the role of MRI in the management of patients with MS. The aim of this review is to summarize the latest insights into the utility of MRI in MS.

scholarly journals Pathogenetical and Neurophysiological Features of Patients with Autism Spectrum Disorder: Phenomena and Diagnoses

2019 ◽  
Vol 8 (10) ◽  
pp. 1588
Author(s):  
Yunho Jin ◽  
Jeonghyun Choi ◽  
Seunghoon Lee ◽  
Jong Won Kim ◽  
Yonggeun Hong
Keyword(s):  
Autism Spectrum Disorder ◽  
Neural Development ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Deficits ◽  
Restricted Interests ◽  
Neuropsychiatric Comorbidities ◽  
The Brain

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is accompanied by social deficits, repetitive and restricted interests, and altered brain development. The majority of ASD patients suffer not only from ASD itself but also from its neuropsychiatric comorbidities. Alterations in brain structure, synaptic development, and misregulation of neuroinflammation are considered risk factors for ASD and neuropsychiatric comorbidities. Electroencephalography has been developed to quantitatively explore effects of these neuronal changes of the brain in ASD. The pineal neurohormone melatonin is able to contribute to neural development. Also, this hormone has an inflammation-regulatory role and acts as a circadian key regulator to normalize sleep. These functions of melatonin may play crucial roles in the alleviation of ASD and its neuropsychiatric comorbidities. In this context, this article focuses on the presumable role of melatonin and suggests that this hormone could be a therapeutic agent for ASD and its related neuropsychiatric disorders.

scholarly journals Plectin in the Central Nervous System and a Putative Role in Brain Astrocytes

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2353
Author(s):  
Maja Potokar ◽  
Jernej Jorgačevski
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Current Knowledge ◽  
Cell Types ◽  
Cellular Proteins ◽  
Bidirectional Communication ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Plectin, a high-molecular-mass cytolinker, is abundantly expressed in the central nervous system (CNS). Currently, a limited amount of data about plectin in the CNS prevents us from seeing the complete picture of how plectin affects the functioning of the CNS as a whole. Yet, by analogy to its role in other tissues, it is anticipated that, in the CNS, plectin also functions as the key cytoskeleton interlinking molecule. Thus, it is likely involved in signalling processes, thereby affecting numerous fundamental functions in the brain and spinal cord. Versatile direct and indirect interactions of plectin with cytoskeletal filaments and enzymes in the cells of the CNS in normal physiological and in pathologic conditions remain to be fully addressed. Several pathologies of the CNS related to plectin have been discovered in patients with plectinopathies. However, in view of plectin as an integrator of a cohesive mesh of cellular proteins, it is important that the role of plectin is also considered in other CNS pathologies. This review summarizes the current knowledge of plectin in the CNS, focusing on plectin isoforms that have been detected in the CNS, along with its expression profile and distribution alongside diverse cytoskeleton filaments in CNS cell types. Considering that the bidirectional communication between neurons and glial cells, especially astrocytes, is crucial for proper functioning of the CNS, we place particular emphasis on the known roles of plectin in neurons, and we propose possible roles of plectin in astrocytes.

scholarly journals Multiple sclerosis: environmental risk factors

1998 ◽  
Vol XXX (1-2) ◽  
pp. 40-42
Author(s):  
Enrico Granieri ◽  
Ilaria Casetta
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Environmental Factors ◽  
Environmental Risk ◽  
Biological Significance ◽  
Unknown Etiology ◽  
Brain And Spinal Cord ◽  
The Brain

Multiple sclerosis is a disease of unknown etiology characterized by inflammory demyelination of the brain and spinal cord. Epidemiological investigations play important role in study of multiple sclerosis. Geographical distribution of the disease has been described in terms of prevalence and incidence. The possible role of environmental factors as a cause of multiple sclerosis had been hypothesized with observation of unequal geographic distribution of the disease. More interesting, in terms of their biological significance, are attempts to identify associations between multiple sclerosis and situations or events wich could cause blood-brain barrier damages, such as trauma or toxic exposures.

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