TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice

AbstractThe mechanisms regulating myelin repair in the adult central nervous system (CNS) are unclear. Here, we identify DNA hydroxymethylation, catalyzed by the Ten-Eleven-Translocation (TET) enzyme TET1, as necessary for myelin repair in young adults and defective in old mice. Constitutive and inducible oligodendrocyte lineage-specific ablation of Tet1 (but not of Tet2), recapitulate this age-related decline in repair of demyelinated lesions. DNA hydroxymethylation and transcriptomic analyses identify TET1-target in adult oligodendrocytes, as genes regulating neuro-glial communication, including the solute carrier (Slc) gene family. Among them, we show that the expression levels of the Na+/K+/Cl− transporter, SLC12A2, are higher in Tet1 overexpressing cells and lower in old or Tet1 knockout. Both aged mice and Tet1 mutants also present inefficient myelin repair and axo-myelinic swellings. Zebrafish mutants for slc12a2b also display swellings of CNS myelinated axons. Our findings suggest that TET1 is required for adult myelin repair and regulation of the axon-myelin interface.

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Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

AGE ◽

10.1007/s11357-011-9365-7 ◽

2012 ◽

Vol 35 (2) ◽

pp. 331-342 ◽

Cited By ~ 15

Author(s):

Elisa Mitiko Kawamoto ◽

Andrea Rodrigues Vasconcelos ◽

Sabrina Degaspari ◽

Ana Elisa Böhmer ◽

Cristoforo Scavone ◽

...

Keyword(s):

Nitric Oxide ◽

Central Nervous System ◽

Nervous System ◽

Cyclic Gmp ◽

Oxidative Status ◽

Age Related ◽

Age Related Changes

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Inflammatory Chemokines Expression Variations and Their Receptors in APP/PS1 Mice

Journal of Alzheimer s Disease ◽

10.3233/jad-210489 ◽

2021 ◽

pp. 1-10

Author(s):

Adrián Jorda ◽

Martin Aldasoro ◽

Constanza Aldasoro ◽

Soraya L. Valles

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Chemokine Receptors ◽

Presenilin 1 ◽

Wild Type ◽

Rt Pcr ◽

New Strategy ◽

Inflammatory Chemokines ◽

Inflammatory Changes ◽

Old Mice

Background: In Alzheimer’s disease (AD), an increase in inflammation is distinctive. Amyloid precursor protein plus presenilin-1 (APP/PS1 mice) is a model for this illness. Chemokines secreted by central nervous system (CNS) cells could play multiple important roles in AD. Data looking for the chemokines involved in inflammatory mechanisms are lacking. To understand the changes that occur in the inflammation process in AD, it is necessary to improve strategies to act on specific inflammatory targets. Objective: Chemokines and their receptors involved in phagocytosis, demyelination, chemotaxis, and coagulation were the objective of our study. Methods: Female APPswe/PS1 double-transgenic mice (B6C3-Tg) were used and cortex brain from 20–22-month-old mice obtained and used to quantify chemokines and chemokine receptors expression using RT-PCR technique. Results: Significant inflammatory changes were detected in APP/PS1 compared to wild type mice. CCR1, CCR3, CCR4, and CCR9 were elevated, and CCR2 were decreased compared with wild type mice. Their ligands CCL7, CCL11, CCL17, CCL22, CCL25, and CXCL4 showed an increase expression; however, changes were not observed in CCL2 in APP/PS1 compared to wild type mice. Conclusion: This change in expression could explain the differences between AD patients and elderly people without this illness. This would provide a new strategy for the treatment of AD, with the possibility to act in specific inflammatory targets.

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Age-Dependent Resistance to Lethal Alphavirus Encephalitis in Mice: Analysis of Gene Expression in the Central Nervous System and Identification of a Novel Interferon-Inducible Protective Gene, Mouse ISG12

Journal of Virology ◽

10.1128/jvi.76.22.11688-11703.2002 ◽

2002 ◽

Vol 76 (22) ◽

pp. 11688-11703 ◽

Cited By ~ 82

Author(s):

Lucia Labrada ◽

Xiao Huan Liang ◽

Wei Zheng ◽

Christine Johnston ◽

Beth Levine

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Virus Infection ◽

Sindbis Virus ◽

Expressed Sequence Tag ◽

Severe Disease ◽

Altered Expression ◽

Age Dependent ◽

Old Mice

ABSTRACT Several different mammalian neurotropic viruses produce an age-dependent encephalitis characterized by more severe disease in younger hosts. To elucidate potential factors that contribute to age-dependent resistance to lethal viral encephalitis, we compared central nervous system (CNS) gene expression in neonatal and weanling mice that were either mock infected or infected intracerebrally with a recombinant strain, dsTE12Q, of the prototype alphavirus Sindbis virus. In 1-day-old mice, infection with dsTE12Q resulted in rapidly fatal disease associated with high CNS viral titers and extensive CNS apoptosis, whereas in 4-week-old mice, dsTE12Q infection resulted in asymptomatic infection with lower CNS virus titers and undetectable CNS apoptosis. GeneChip expression comparisons of mock-infected neonatal and weanling mouse brains revealed developmental regulation of the mRNA expression of numerous genes, including some apoptosis regulatory genes, such as the proapoptotic molecules caspase-3 and TRAF4, which are downregulated during development, and the neuroprotective chemokine, fractalkine, which is upregulated during postnatal development. In parallel with increased neurovirulence and increased viral replication, Sindbis virus infection in 1-day-old mice resulted in both a greater number of host inflammatory genes with altered expression and greater changes in levels of host inflammatory gene expression than infection in 4-week-old mice. Only one inflammatory response gene, an expressed sequence tag similar to human ISG12, increased by a greater magnitude in infected 4-week-old mouse brains than in infected 1-day-old mouse brains. Furthermore, we found that enforced neuronal ISG12 expression results in a significant delay in Sindbis virus-induced death in neonatal mice. Together, our data identify genes that are developmentally regulated in the CNS and genes that are differentially regulated in the brains of different aged mice in response to Sindbis virus infection.

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Molecular Biology of Vertebrate Olfactory Receptors and Circuits

Oxford Research Encyclopedia of Neuroscience ◽

10.1093/acrefore/9780190264086.013.92 ◽

2021 ◽

Author(s):

Richard P. Tucker ◽

Qizhi Gong

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Olfactory Bulb ◽

Gene Family ◽

Sensory Neuron ◽

Sensory Neurons ◽

Odorant Receptor ◽

Vomeronasal Organ ◽

Odorant Receptors ◽

The Central Nervous System

Animals use their olfactory system for the procurement of food, the detection of danger, and the identification of potential mates. In vertebrates, the olfactory sensory neuron has a single apical dendrite that is exposed to the environment and a single basal axon that projects to the central nervous system (i.e., the olfactory bulb). The first odorant receptors to be discovered belong to an enormous gene family encoding G protein-coupled seven transmembrane domain proteins. Odorant binding to these classical odorant receptors initiates a GTP-dependent signaling cascade that uses cAMP as a second messenger. Subsequently, additional types of odorant receptors using different signaling pathways have been identified. While most olfactory sensory neurons are found in the olfactory sensory neuroepithelium, others are found in specialized olfactory subsystems. In rodents, the vomeronasal organ contains neurons that recognize pheromones, the septal organ recognizes odorant and mechanical stimuli, and the neurons of the Grüneberg ganglion are sensitive to cool temperatures and certain volatile alarm signals. Within the olfactory sensory neuroepithelium, each sensory neuron expresses a single odorant receptor gene out of the large gene family; the axons of sensory neurons expressing the same odorant receptor typically converge onto a pair of glomeruli at the periphery of the olfactory bulb. This results in the transformation of olfactory information into a spatially organized odortopic map in the olfactory bulb. The axons originating from the vomeronasal organ project to the accessory olfactory bulb, whereas the axons from neurons in the Grüneberg ganglion project to 10 specific glomeruli found in the caudal part of the olfactory bulb. Within a glomerulus, the axons originating from olfactory sensory neurons synapse on the dendrites of olfactory bulb neurons, including mitral and tufted cells. Mitral cells and tufted cells in turn project directly to higher brain centers (e.g., the piriform cortex and olfactory tubercle). The integration of olfactory information in the olfactory cortices and elsewhere in the central nervous system informs and directs animal behavior.

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Ecstasy-Associated Pneumomediastinum

Annals of The Royal College of Surgeons of England ◽

10.1308/003588407x183373 ◽

2007 ◽

Vol 89 (4) ◽

pp. 389-393 ◽

Cited By ~ 19

Author(s):

Silvana F Marasco ◽

H Kiat Lim

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Young Adults ◽

Inner City ◽

Physical Exertion ◽

Pharmacological Effect ◽

Valsalva Manoeuvre ◽

The Hours ◽

History Of ◽

The Central Nervous System

INTRODUCTION Ecstasy, also known as MDMA (3,4, methylenedioxymethamphetamine), is a popular illicit party drug amongst young adults. The drug induces a state of euphoria secondary to its stimulant activity in the central nervous system. PATIENTS AND METHODS A database review at two major inner city hospitals was undertaken to identify patients presenting with pneumomediastinum and their charts reviewed. A Medline review of all reported cases of pneumomediastinum associated with ecstasy abuse was undertaken. RESULTS A total of 56 patients presenting with pneumomediastinum were identified over a 5-year period. Review of the charts revealed a history of ecstasy use in the hours prior to presentation in six of these patients, representing the largest series reported to date. CONCLUSIONS Review of previously reported cases reveals the likely mechanism is due to Valsalva manoeuvre during periods of extreme physical exertion, and not a direct pharmacological effect of the drug.

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Leukemia inhibitory factor signaling modulates both central nervous system demyelination and myelin repair

Glia ◽

10.1002/glia.20646 ◽

2008 ◽

Vol 56 (6) ◽

pp. 686-698 ◽

Cited By ~ 53

Author(s):

Mark P. Marriott ◽

Ben Emery ◽

Holly S. Cate ◽

Michele D. Binder ◽

Dennis Kemper ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Leukemia Inhibitory Factor ◽

Inhibitory Factor ◽

Myelin Repair ◽

Central Nervous System Demyelination

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Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Light Chain Repertoire

Infection and Immunity ◽

10.1128/iai.73.11.7477-7484.2005 ◽

2005 ◽

Vol 73 (11) ◽

pp. 7477-7484 ◽

Cited By ~ 15

Author(s):

S. Louise Smithson ◽

Kris Kolibab ◽

Anne K. Shriner ◽

Neeti Srivastava ◽

Sadik Khuder ◽

...

Keyword(s):

Young Adults ◽

Gene Family ◽

Light Chain ◽

Vaccine Efficacy ◽

The Elderly ◽

Chain Gene ◽

Light Chain Gene ◽

Age Related ◽

Gene Usage ◽

Variable Light

ABSTRACT Streptococcus pneumoniae is a human bacterial pathogen responsible for serious infections including pneumonia. The currently licensed polysaccharide vaccine provides 60 to 80% protection in young adults, but in the elderly the vaccine efficacy is drastically reduced despite normal antibody levels. We hypothesized that the reduced vaccine efficacy in the elderly results from altered variable gene family usage. We have analyzed the light chain gene usage in 20 young (20 to 30 years of age) and 20 elderly (65 to 86 years of age) adults in response to pneumococcal polysaccharide 4 (PPS4) and PPS14. We generated a variable light chain library using B cells specific for PPS4 and PPS14 from each vaccinated individual. We determined complete sequences and somatic mutation frequencies in all isolated variable light chain fragments. Six gene families, κ1, κ2, κ3, κ4, λ1, and λ3, were identified in response to PPS4 and PPS14 in both age groups. Comparison of young and elderly adults demonstrated significant differences in κ4, λ1, and λ3 gene usage in response to PPS4 and PPS14. With aging, there was a significant increase in κ4 gene usage and a significant decrease in λ1 and λ3 gene usage in response to both PPS4 and PPS14. Although both Vκ1 and Vλ3 gene products demonstrated extensive mutations, there was no age-related difference in mutational frequency per gene family. These findings suggest an age-related change in light chain gene usage in response to PPS4 and PPS14.

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