scholarly journals Synaptic silencing affects the density and complexity of oligodendrocyte precursor cells in the adult mouse hippocampus

2020 ◽  
Author(s):  
Irene Chacon-De-La-Rocha ◽  
Gemma L. Fryatt ◽  
Andrea D. Rivera ◽  
Laura Restani ◽  
Matteo Caleo ◽  
...  
Keyword(s):  
Botulinum Neurotoxin ◽  
Adult Mouse ◽  
Synaptic Activity ◽  
Oligodendrocyte Progenitor Cells ◽  
Adult Mice ◽  
Proliferation And Differentiation ◽  
Mouse Hippocampus ◽  
Network Plasticity ◽  
Oligodendrocyte Precursor ◽  
Cellular Integrity

AbstractOligodendrocyte progenitor cells (OPCs) are responsible for generating oligodendrocytes, the myelinating cells of the CNS. Life-long myelination is promoted by neuronal activity and is essential for neural network plasticity and learning. OPCs are known to contact synapses and it is proposed that neuronal synaptic activity in turn regulates OPC proliferation and differentiation. To examine this in the adult, we performed unilateral injection of the synaptic blocker botulinum neurotoxin A (BoNT/A) into the hippocampus of adult mice. We confirm BoNT/A cleaves SNAP-25 in the CA1 are of the hippocampus, which has been proven to block neurotransmission. Notably, synaptic silencing by BoNT/A significantly decreased OPC density and caused their shrinkage, as determined by immunolabelling for the OPC marker NG2. Inhibition of synaptic activity resulted in an overall decrease in the number of OPC processes, as well as a decrease in their lengths and branching frequency. These data indicate that synaptic activity is important for maintaining adult OPC numbers and cellular integrity, which is relevant to pathological scenarios characterized by decreased synaptic activity.

scholarly journals Teriflunomide Promotes Oligodendroglial 8,9-Unsaturated Sterol Accumulation and CNS Remyelination

2021 ◽  
Vol 8 (6) ◽  
pp. e1091
Author(s):  
Elodie Martin ◽  
Marie-Stephane Aigrot ◽  
Foudil Lamari ◽  
Corinne Bachelin ◽  
Catherine Lubetzki ◽  
...  
Keyword(s):  
Oligodendrocyte Differentiation ◽  
Oxidosqualene Cyclase ◽  
Adult Mice ◽  
Low Concentrations ◽  
Proliferation And Differentiation ◽  
Glial Cultures ◽  
Oligodendrocyte Precursor ◽  
Target Effect

Background and ObjectivesTo test whether low concentrations of teriflunomide (TF) could promote remyelination, we investigate the effect of TF on oligodendrocyte in culture and on remyelination in vivo in 2 demyelinating models.MethodsThe effect of TF on oligodendrocyte precursor cell (OPC) proliferation and differentiation was assessed in vitro in glial cultures derived from neonatal mice and confirmed on fluorescence-activated cell sorting–sorted adult OPCs. The levels of the 8,9-unsaturated sterols lanosterol and zymosterol were quantified in TF- and sham-treated cultures. In vivo, TF was administered orally, and remyelination was assessed both in myelin basic protein–GFP-nitroreductase (Mbp:GFP-NTR) transgenic Xenopus laevis demyelinated by metronidazole and in adult mice demyelinated by lysolecithin.ResultsIn cultures, low concentrations of TF down to 10 nM decreased OPC proliferation and increased their differentiation, an effect that was also detected on adult OPCs. Oligodendrocyte differentiation induced by TF was abrogated by the oxidosqualene cyclase inhibitor Ro 48-8071 and was mediated by the accumulation of zymosterol. In the demyelinated tadpole, TF enhanced the regeneration of mature oligodendrocytes up to 2.5-fold. In the mouse demyelinated spinal cord, TF promoted the differentiation of newly generated oligodendrocytes by a factor of 1.7-fold and significantly increased remyelination.DiscussionTF enhances zymosterol accumulation in oligodendrocytes and CNS myelin repair, a beneficial off-target effect that should be investigated in patients with multiple sclerosis.

scholarly journals Oligodendrocyte Progenitor Cells Increase Chi3l1 Secretion in exosome to Activate Myh9 and Promote Proliferation through Connexin47 Connected to Astrocytes

2020 ◽  
Author(s):  
Lu Jiang ◽  
Xiaoyan Zhang ◽  
Dan Xu ◽  
Wenjin Zhang ◽  
GuoGuang Peng ◽  
...  
Keyword(s):  
Direct Contact ◽  
Neurological Diseases ◽  
The Elderly ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Nanoparticle Tracking Analysis ◽  
Gap Junction Channel ◽  
Proliferation And Differentiation ◽  
Sirna Interference ◽  
Oligodendrocyte Precursor

Abstract Background: Neurodegenerative diseases, caused by the loss of neurons or myelin sheath, are some of the most important neurological diseases that threaten the health of the elderly. In the CNS, oligodendrocytes (OLs) are the only cells that can form myelin. Astrocytes (ASTs) play a generally beneficial role in remyelination, including the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) to OLs. However, the specific downstream mechanism is unclear.Methods: This study investigated the proliferation of OPCs in OPCs mono-culture, OPCs culture with ASTs supernatant, and ASTs-OPCs co-culture. Gene Ontology (GO) analysis were used to analyze the differentially expressed genes after transcriptome sequencing of these OPCs. Electron microscope, Nanoparticle Tracking Analysis (NTA), Fluorescence tracing of exosomes and Western blot were used to evaluate the effects of exsomes. Pull-down, co-immunoprecipitation (Co-IP) and mass spectrometry analys were conducted to find the downstream signal proliferation which is transmitted information into OPCs.Reasults: Direct contact co-culture of ASTs and OPCs promotes the proliferation of OPCs. After Cx47 siRNA interference under ASTs-OPCs co-culture, Chi3l1 secretion in exosome reveals associated decrease, and OPCs proliferation decreased. The cell proliferation induced by Chi3l1 was inhibited after siRNA interfered with Myh9, and the expression of cyclin D1 was also decreased.Conclusions: These results suggest that ASTs transmit information to OPCs by increasing gap junction channel Cx47, thereby promoting the secretion of Chi3l1 in exosome of OPCs. The secretory form of Chi3l1 in exosome might be easier to enter the target cell than in extracellular supernatant, which is beneficial to the activation of Myh9 to promote OPCs proliferation. This may be a potential target for drugs rescuing neurodegeneration diseases related to remyelination.

scholarly journals Oligodendrocyte Progenitor Cells Increase Chi3l1 Secretion in Exosome to Activate Myh9 and Promote Proliferation through Connexin47 Connected to Astrocytes

2020 ◽  
Author(s):  
Lu Jiang ◽  
XIAOYAN ZHANG ◽  
Dan Xu ◽  
Wenjin Zhang ◽  
GuoGuang Peng ◽  
...  
Keyword(s):  
Direct Contact ◽  
Neurological Diseases ◽  
The Elderly ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Nanoparticle Tracking Analysis ◽  
Gap Junction Channel ◽  
Proliferation And Differentiation ◽  
Sirna Interference ◽  
Oligodendrocyte Precursor

Abstract Background: Neurodegenerative diseases, caused by the loss of neurons or myelin sheath, are some of the most important neurological diseases that threaten the health of the elderly. In the CNS, oligodendrocytes (OLs) are the only cells that can form myelin. Astrocytes (ASTs) play a generally beneficial role in remyelination, including the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) to OLs. However, the specific downstream mechanism is unclear.Methods: This study investigated the proliferation of OPCs in OPCs mono-culture, OPCs culture with ASTs supernatant, and ASTs-OPCs co-culture. Gene Ontology (GO) analysis were used to analyze the differentially expressed genes after transcriptome sequencing of these OPCs. Electron microscope, Nanoparticle Tracking Analysis (NTA), Fluorescence tracing of exosomes and Western blot were used to evaluate the effects of exsomes. Pull-down, co-immunoprecipitation (Co-IP) and mass spectrometry analys were conducted to find the downstream signal proliferation which is transmitted information into OPCs.Reasults: Direct contact co-culture of ASTs and OPCs promotes the proliferation of OPCs. After Cx47 siRNA interference under ASTs-OPCs co-culture, Chi3l1 secretion in exosome reveals associated decrease, and OPCs proliferation decreased. The cell proliferation induced by Chi3l1 was inhibited after siRNA interfered with Myh9, and the expression of cyclin D1 was also decreased.Conclusions: These results suggest that ASTs transmit information to OPCs by increasing gap junction channel Cx47, thereby promoting the secretion of Chi3l1 in exosome of OPCs. The secretory form of Chi3l1 in exosome might be easier to enter the target cell than in extracellular supernatant, which is beneficial to the activation of Myh9 to promote OPCs proliferation. This may be a potential target for drugs rescuing neurodegeneration diseases related to remyelination.

scholarly journals The long noncoding RNA Synage regulates synapse stability and neuronal function in the cerebellum

2021 ◽  
Author(s):  
Fei Wang ◽  
Qianqian Wang ◽  
Baowei Liu ◽  
Lisheng Mei ◽  
Sisi Ma ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Cerebellar Atrophy ◽  
Synaptic Activity ◽  
Motor Dysfunction ◽  
Cerebellar Development ◽  
Full Spectrum ◽  
Density Reduction ◽  
Adult Mice ◽  
Synapse Density ◽  
And Function

AbstractThe brain is known to express many long noncoding RNAs (lncRNAs); however, whether and how these lncRNAs function in modulating synaptic stability remains unclear. Here, we report a cerebellum highly expressed lncRNA, Synage, regulating synaptic stability via at least two mechanisms. One is through the function of Synage as a sponge for the microRNA miR-325-3p, to regulate expression of the known cerebellar synapse organizer Cbln1. The other function is to serve as a scaffold for organizing the assembly of the LRP1-HSP90AA1-PSD-95 complex in PF-PC synapses. Although somewhat divergent in its mature mRNA sequence, the locus encoding Synage is positioned adjacent to the Cbln1 loci in mouse, rhesus macaque, and human, and Synage is highly expressed in the cerebella of all three species. Synage deletion causes a full-spectrum cerebellar ablation phenotype that proceeds from cerebellar atrophy, through neuron loss, on to synapse density reduction, synaptic vesicle loss, and finally to a reduction in synaptic activity during cerebellar development; these deficits are accompanied by motor dysfunction in adult mice, which can be rescued by AAV-mediated Synage overexpression from birth. Thus, our study demonstrates roles for the lncRNA Synage in regulating synaptic stability and function during cerebellar development.

Oral Infectivity of Vibrio vulnificus in Suckling Mice

1987 ◽  
Vol 50 (12) ◽  
pp. 1013-1016 ◽  
Author(s):  
ANTOLIN L. REYES ◽  
CLIFFORD H. JOHNSON ◽  
PROCTER L. SPAULDING ◽  
GERARD N. STELMA
Keyword(s):  
Adult Mouse ◽  
Vibrio Vulnificus ◽  
Close Correlation ◽  
Oral Route ◽  
Environmental Isolates ◽  
Suckling Mice ◽  
Virulent Isolate ◽  
Adult Mice ◽  
Lethal Doses ◽  
Intraperitoneal Inoculation

Lethal doses of 11 clinical and environmental isolates of Vibrio vulnificus were determined in suckling mice after oral challenge. With one exception, isolates that were virulent to iron-overloaded adult mice after intraperitoneal inoculation were highly lethal to the infant mice (>50% lethality at 105 CFU/mouse). The virulent isolate that failed to kill infant mice at 105 CFU had lost its invasiveness. Conditionally virulent isolates that were virulent only to simultaneously iron-overloaded and immunosuppressed adult mice required > 109 CFU to kill the infant mice. Avirulent isolates failed to kill at >109 CFU/mouse. There were no significant differences in the lethalities of clinical and environmental isolates. These findings demonstrated a close correlation between virulence in the iron-overloaded adult mouse and infectivity by the oral route.

scholarly journals Inversions produced during V(D)J rearrangement at IgH, the immunoglobulin heavy-chain locus.

1995 ◽  
Vol 15 (2) ◽  
pp. 671-681 ◽  
Author(s):  
A E Sollbach ◽  
G E Wu
Keyword(s):  
Heavy Chain ◽  
Adult Mouse ◽  
Fetal Liver ◽  
Immunoglobulin Heavy Chain ◽  
Antigen Receptors ◽  
Adult Mice ◽  
Chain Locus ◽  
Heavy Chain Locus ◽  
Fetal Liver Cells

Diversity in immunoglobulin antigen receptors is generated in part by V(D)J recombination. In this process, different combinations of gene elements are joined in various configurations. Products of V(D)J recombination are coding joints, signal joints, and hybrid junctions, which are generated by deletion or inversion. To determine their role in the generation of diversity, we have examined two sorts of recombination products, coding joints and hybrid junctions, that have formed by inversion at the mouse immunoglobulin heavy-chain locus. We developed a PCR assay for quantification and characterization of inverted rearrangements of DH and JH gene elements. In primary cells from adult mice, inverted DJH rearrangements are detectable but they are rare. There were approximately 1,100 to 2,200 inverted DJH coding joints and inverted DJH hybrid junctions in the marrow of one adult mouse femur. On day 16 of gestation, inverted DJH rearrangements are more abundant. There are approximately 20,000 inverted DJH coding joints and inverted DJH hybrid junctions per day 16 fetal liver. In fetal liver cells, the number of inverted DJH rearrangements remains relatively constant from day 14 to day 16 of gestation. Inverted DJH rearrangements to JH4, the most 3' JH element, are more frequently detected than inverted DJH rearrangements to other JH elements. We compare the frequencies of inverted DJH rearrangements to previously determined frequencies of uninverted DJH rearrangements (DJH rearrangements formed by deletion). We suggest that inverted DJH rearrangements are influenced by V(D)J recombination mechanistic constraints and cellular selection.

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