Trends in neurosciences
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Neuropathic and inflammatory pain promote a large number of persisting adaptations at the cellular and molecular level, allowing even transient tissue or nerve damage to elicit changes in cells that contribute to the development of chronic pain and associated symptoms. There is evidence that injury-induced changes in chromatin structure drive stable changes in gene expression and neural function, which may cause several symptoms, including allodynia, hyperalgesia, anxiety, and depression. Recent findings on epigenetic changes in the spinal cord and brain during chronic pain may guide fundamental advances in new treatments. Here, we provide a brief overview of epigenetic regulation in the nervous system and then discuss the still-limited literature that directly implicates epigenetic modifications in chronic pain syndromes.
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Trends in neurosciences · Feb 2015
ReviewCerebral cortex assembly: generating and reprogramming projection neuron diversity.
The mammalian cerebral cortex is responsible for the highest levels of associative, cognitive and motor functions. In the central nervous system (CNS) the cortex stands as a prime example of extreme neuronal diversity, broadly classified into excitatory projection neurons (PNs) and inhibitory interneurons (INs). We review here recent progress made in understanding the strategies and mechanisms that shape PN diversity during embryogenesis, and discuss how PN classes may be maintained, postnatally, for the life of the organism. In addition, we consider the intriguing possibility that PNs may be amenable to directed reprogramming of their class-specific features to allow enhanced cortical plasticity in the adult.
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Trends in neurosciences · Dec 2014
ReviewLost after translation: missorting of Tau protein and consequences for Alzheimer disease.
Tau is a microtubule-associated-protein that is sorted into neuronal axons in physiological conditions. In Alzheimer disease (AD) and other tauopathies, Tau sorting mechanisms fail and Tau becomes missorted into the somatodendritic compartment. In AD, aberrant amyloid-β (Aβ) production might trigger Tau missorting. ⋯ Disease-associated missorting of Tau is connected to increased phosphorylation and aggregation of Tau, and impaired microtubule interactions. Disease-causing mechanisms involve impaired transport, aberrant kinase activation, non-physiological interactions of Tau, and prion-like spreading. In this review we focus on the physiological and pathological (mis)sorting of Tau, the underlying mechanisms, and effects in disease.
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Chronic pain represents a major challenge to clinical practice and basic science. Excitatory neurotransmission in somatosensory nociceptive pathways is predominantly mediated by glutamatergic synapses. A key feature of these synapses is their ability to adapt synaptic strength in an activity-dependent manner. ⋯ Recent work has recognized that synaptic plasticity at both excitatory and inhibitory synapses can function as a prime mechanism underlying pathological pain. In this review, cellular and molecular mechanisms underlying synaptic plasticity in nociceptive pathways will be reviewed and discussed. New insights derived from these advances are expected to expedite development of novel interventional approaches for treatment of pathological pain.
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Trends in neurosciences · May 2014
ReviewZebrafish models for translational neuroscience research: from tank to bedside.
The zebrafish (Danio rerio) is emerging as a new important species for studying mechanisms of brain function and dysfunction. Focusing on selected central nervous system (CNS) disorders (brain cancer, epilepsy, and anxiety) and using them as examples, we discuss the value of zebrafish models in translational neuroscience. ⋯ Outlining the role of zebrafish in modeling a wide range of human brain disorders, we also summarize recent applications and existing challenges in this field. Finally, we emphasize the potential of zebrafish models in behavioral phenomics and high-throughput genetic/small molecule screening, which is critical for CNS drug discovery and identifying novel candidate genes.