Advances in epigenetics link genetics to the environment and disease

Nature, Год журнала: 2019, Номер 571(7766), С. 489 - 499

Опубликована: Июль 1, 2019

Язык: Английский

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Innate immune memory in the brain shapes neurological disease hallmarks

Nature, Год журнала: 2018, Номер 556(7701), С. 332 - 338

Опубликована: Апрель 1, 2018

Язык: Английский

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Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior

Cell Reports, Год журнала: 2018, Номер 22(8), С. 2216 - 2225

Опубликована: Фев. 1, 2018

To understand the cellular basis of behavior, it is necessary to know cell types that exist in nervous system and their contributions function. Spinal networks are essential for sensory processing motor behavior provide a powerful identifying correlates behavior. Here, we used massively parallel single nucleus RNA sequencing (snRNA-seq) create an atlas adult mouse lumbar spinal cord. We identified molecularly characterized 43 neuronal populations. Next, leveraged snRNA-seq approach unbiased identification populations were active following using transcriptional signature activity. This can be future link gene expression data with dynamic biological responses injury, disease.

Язык: Английский

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Is plasticity of synapses the mechanism of long-term memory storage?

npj Science of Learning, Год журнала: 2019, Номер 4(1)

Опубликована: Июль 2, 2019

Abstract It has been 70 years since Donald Hebb published his formalized theory of synaptic adaptation during learning. Hebb’s seminal work foreshadowed some the great neuroscientific discoveries following decades, including discovery long-term potentiation and other lasting forms plasticity, more recently residence memories in synaptically connected neuronal assemblies. Our understanding processes underlying learning memory dominated by view that synapses are principal site information storage brain. This received substantial support from research several model systems, with vast majority studies on topic corroborating a role for storage. Yet, despite neuroscience community’s best efforts, we still without conclusive proof reside at synapses. Furthermore, an increasing number non-synaptic mechanisms have emerged also capable acting as substrates. In this review, address key findings plasticity literature make these phenomena such attractive mechanisms. We then turn our attention to evidence questions reliance exclusively changes synapse attempt integrate opposing views.

Язык: Английский

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Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions

Nature Communications, Год журнала: 2018, Номер 9(1)

Опубликована: Окт. 8, 2018

The turnover of brain proteins is critical for organism survival, and its perturbations are linked to pathology. Nevertheless, protein lifetimes have been difficult obtain in vivo. They readily measured vitro by feeding cells with isotopically labeled amino acids, followed mass spectrometry analyses. In vivo generated from at least two sources: acids the diet, non-labeled degradation pre-existing proteins. This renders measurements difficult. Here we solved this problem rigorously a workflow that combines mouse isotopic labeling, spectrometry, mathematical modeling. We also established several independent approaches test validate results. enabled us measure accurate ~3500 high precision our data provided large set biologically significant observations, including pathway-, organelle-, organ-, or cell-specific effects, along comprehensive catalog extremely long-lived (ELLPs).

Язык: Английский

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Myelin Sheath as a Dielectric Waveguide for Signal Propagation in the Mid‐Infrared to Terahertz Spectral Range

Advanced Functional Materials, Год журнала: 2018, Номер 29(7)

Опубликована: Дек. 27, 2018

Abstract The myelin sheath enables dramatic speed enhancement for signal propagation in nerves. In this work, myelinated nerve structure is experimentally and theoretically studied using synchrotron‐radiation‐based Fourier‐transform infrared microspectroscopy. It found that, with a certain mid‐infrared to terahertz spectral range, the possesses ≈2‐fold higher refraction index compared outer medium or inner axon, suggesting that can serve as an dielectric waveguide. By calculating correlation between material characteristics of radical energy distribution nerves, it demonstrated sheath, normal thickness (≈2 µm) constant nature, confine field within enable at millimeter scale without loss. supplied amplified when crossing nodes Ranvier via periodic relay. These findings provide first model explaining mechanism neurotransmission through which may promote development biological‐tissue label‐free detection, biomaterial‐based sensors, neural information, noninvasive brain–machine interfaces.

Язык: Английский

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Neuroprotective Actions of Dietary Choline

Nutrients, Год журнала: 2017, Номер 9(8), С. 815 - 815

Опубликована: Июль 28, 2017

Choline is an essential nutrient for humans. It a precursor of membrane phospholipids (e.g., phosphatidylcholine (PC)), the neurotransmitter acetylcholine, and via betaine, methyl group donor S-adenosylmethionine. High choline intake during gestation early postnatal development in rat mouse models improves cognitive function adulthood, prevents age-related memory decline, protects brain from neuropathological changes associated with Alzheimer’s disease (AD), neurological damage epilepsy, fetal alcohol syndrome, inherited conditions such as Down Rett syndromes. These effects are correlated modifications histone DNA methylation brain, alterations expression genes that encode proteins important learning processing, suggesting possible epigenomic mechanism action. Dietary adult may also influence effect on PC containing eicosapentaenoic docosahexaenoic acids; polyunsaturated species whose levels reduced brains AD patients, higher performance, resistance to decline.

Язык: Английский

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DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress

Nature Communications, Год журнала: 2017, Номер 8(1)

Опубликована: Окт. 18, 2017

Chemical modifications on DNA molecules, such as 5-methylcytosine and 5-hydroxymethylcytosine, play important roles in the mammalian brain. A novel adenine modification, N(6)-methyladenine (6mA), has recently been found cells. However, presence function(s) of 6mA brain remain unclear. Here we demonstrate dynamics mouse response to environmental stress. We find that overall levels are significantly elevated upon Genome-wide transcriptome profiling reveal an inverse association between dynamic changes a set upregulated neuronal genes or downregulated LINE transposon expression. Genes bearing stress-induced overlap with loci associated neuropsychiatric disorders. These results suggest epigenetic role for well its potential involvement N6-methyladenine is covalent modification genome. Here, Yao colleagues show level following stress, subsequent differential gene expression correlated

Язык: Английский

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Histone H3 lysine K4 methylation and its role in learning and memory

Epigenetics & Chromatin, Год журнала: 2019, Номер 12(1)

Опубликована: Янв. 7, 2019

Epigenetic modifications such as histone methylation permit change in chromatin structure without accompanying the underlying genomic sequence. A number of studies animal models have shown that dysregulation various components epigenetic machinery causes cognitive deficits at behavioral level, suggesting proper control is necessary for fundamental processes learning and memory. Histone H3 lysine K4 (H3K4) comprises one component control, global levels this mark are increased hippocampus during memory formation. Modifiers H3K4 needed formation, through studies, many same modifiers mutated human diseases. Indeed, all known methyltransferases four six demethylases been associated with impaired cognition a neurologic or psychiatric disorder. Cognitive impairment patients often manifests intellectual disability, consistent role As modification quintessentially, but not exclusively, transcriptional activity, provides unique insights into regulatory complexity writing, reading, erasing marks within an activated neuron. The following review will discuss connect it to events required developed nervous system. This include initial discussion most recent advances developing methodology analyze methylation, namely mass spectrometry deep sequencing, well how these methods can be applied more deeply understand biology brain. We then introduce core enzymatic mediating addition removal resulting signatures throughout neuronal genome. next foray brain, discussing changes formation retrieval, correlates methyltransferase deficiency region. Finally, we diseases connected each modulator summarize drugs target them.

Язык: Английский

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Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes

Cell Reports, Год журнала: 2019, Номер 26(5), С. 1174 - 1188.e5

Опубликована: Янв. 1, 2019

Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters enhancers of activity-regulated genes. Exactly how modulates these genes has remained unknown. We used single-cell situ transcriptional analysis to show that Fos Npas4 are transcribed stochastic bursts mouse neurons membrane depolarization mRNA expression by increasing burst frequency. then expressed dCas9-p300 or dCas9-HDAC8 fusion proteins mimic block activity-induced locally enhancers. Adding increased prolonging duration resulted higher protein levels an elevation resting potential. Inhibiting reduced reducing frequency impaired experience-dependent induction the hippocampus vivo. Thus, tunes dynamics experience-regulated affect selective changes neuronal cellular function.

Язык: Английский

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