Neuroscience
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Human adult dental pulp stem cells (DPSCs) are self-renewing stem cells that originate from the neural crest during development and remain within the dental pulp niche through adulthood. Due to their multi-lineage differentiation potential and their relative ease of access they represent an exciting alternative for autologous stem cell-based therapies in neurodegenerative diseases. In animal models, DPSCs transplanted into the brain differentiate into functional neurons or astrocytes in response to local environmental cues that appear to influence the fate of the surviving cells. ⋯ This response could not be reproduced when conditioned media from Müller-enriched primary cultures was used. Finally, quantitative RT-PCR was performed to compare the relative expression of glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in DPSC co-cultured with retinal organotypic explants, where BDNF mRNA expression was significantly upregulated in retinal-exposed cultures. Our data demonstrate that DPSC cultures respond to cues from the rat retina and differentiate to express retinal neuronal markers.
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Review
Protein trafficking from synapse to nucleus in control of activity-dependent gene expression.
Long-lasting changes in neuronal excitability require activity-dependent gene expression and therefore the transduction of synaptic signals to the nucleus. Synaptic activity is rapidly relayed to the nucleus by membrane depolarization and the propagation of Ca(2+)-waves. ⋯ Potential mechanisms for active retrograde transport and nuclear targets for these proteins have been identified and recent reports assigned first functions to this type of long-distance signaling. In this review we will discuss how the dissociation of synapto-nuclear protein messenger from synaptic and extrasynaptic sites, their transport, nuclear import and the subsequent genomic response relate to the prevailing concept behind this signaling mechanism, the encoding of signals at their site of origin and their decoding in the nucleus.
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It has been half a century since brain volume enlargement was first reported in animals reared in an enriched environment (EE). As EE animals show improved memory task performance, exposure to EE has been a useful model system for studying the effects of experience on brain plasticity. ⋯ The review is organized in three large domains of changes: anatomical, electrophysiological, and molecular changes. Finally, we discuss open issues and future outlook toward better understanding of EE-induced neural changes.
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CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance, reward, and dependence/withdrawal. Such effects are mediated by opioid signaling at toll-like receptor 4 (TLR4), presumptively of glial origin. Whether CNS endothelial cells express TLR4 is controversial. ⋯ Finally, endothelial cell TLR4 activation by lipopolysaccharide and/or M3G was blocked by the glial inhibitors AV1013 and propentofylline, demonstrating endothelial cells as a new target of such drugs. These data indicate that (-)-morphine and M3G can activate CNS endothelial cells via TLR4, inducing proinflammatory, biochemical, morphological, and behavioral sequelae. CNS endothelial cells may have previously unanticipated roles in opioid-induced effects, in phenomena blocked by presumptive glial inhibitors, as well as TLR4-mediated phenomena more broadly.
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Adrenomedullin (AM) belongs to a calcitonin gene-related peptide (CGRP) family and has been demonstrated to recruit CGRP following chronic use of morphine and neuronal nitric oxide synthase (nNOS) in inflammation. The present study investigated the possibility that AM initiates the changes of other molecules contributing to the development of morphine tolerance in its chronic use. Intrathecal (i.t.) co-administration of the AM receptor antagonist AM22-52 (35.8 μg) inhibited tolerance to morphine-induced analgesia while a daily injection of the AM receptor agonist AM1-50 (8 μg, i.t., bolus) for 9 days induced a decrease in the potency of morphine analgesia and thermal hyperalgesia. ⋯ Particularly, the co-administration of AM22-52 (35.8 μg) inhibited the morphine-induced alterations in nNOS and BAM22. These results indicated that the increase in nNOS and CGRP expressions and the decrease in BAM22 were attributed to the increased AM receptor signaling induced by chronic morphine. The present study supports the hypothesis that the enhancement of AM bioactivity triggered upregulation of pronociceptive mediators and downregulation of pain-inhibiting molecule in a cascade contributing to the development of morphine tolerance.