Neuroscience
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Oligodendrocyte progenitor cells (OPCs) have the ability to divide or to growth arrest and differentiate into myelinating oligodendrocytes in the developing brain. Due to their high number and the persistence of their proliferative capacity in the adult brain, OPCs are being studied as potential targets for myelin repair and also as a potential source of brain tumors. This study addresses the molecular mechanisms regulating the transcriptional changes occurring at the critical transition between proliferation and cell cycle exit in cultured OPCs. ⋯ H2afz). Silencing of c-Myc was associated with decreased histone acetylation at target gene promoters and consequent decrease of gene transcripts. c-Myc silencing also induced a global increase of repressive histone methylation and premature peripheral nuclear chromatin compaction while promoting the progression towards differentiation. We conclude that c-Myc is an important modulator of the transition between proliferation and differentiation of OPCs, although its decrease is not sufficient to induce progression into a myelinating phenotype.
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Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. ⋯ Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio.
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The CNS white matter makes up about half of the human brain, and with advances in human imaging it is increasingly becoming clear that changes in the white matter play a major role in shaping human behavior and learning. However, the mechanisms underlying these white matter changes remain poorly understood. ⋯ Collaboration between fields is essential to understand the function of the white matter, but due to differences in methods and field-specific 'language', communication is often hindered. In this review, we try to address this hindrance by introducing the methods and providing a basic background to myelin biology and human imaging as a prelude to the other reviews within this special issue.
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Alterations in cerebrovascular structure and function may underlie the most common age-associated cognitive, psychiatric, and neurological conditions presented by older adults. Although much remains to understand, existing research suggests several age-associated detrimental conditions may be mediated through sometimes subtle small vessel-induced damage to the cerebral white matter. Here we review a selected portion of the vast work that demonstrates links between changes in vascular and neural health as a function of advancing age, and how even changes in low-to-moderate risk individuals, potentially beginning early in the adult age-span, may have an important impact on functional status in late life.