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Diverse proteins of the denegerin/epithelial sodium channel (DEG/ENa(+) C) superfamily, in particular those belonging to the acid-sensing ion channel (ASIC) family, as well as some members of the transient receptor protein (TRP) channel, function as mechanosensors or may be required for mechanosensation in a diverse range of species and cell types. Therefore, we investigated the putative mechanosensitive function of human odontoblasts using immunohistochemistry to detect ENa(+) C subunits (α, β, and γ) and ASIC (1, 2, 3, and 4) proteins, as well as TRPV4, in these cells. Positive and specific immunoreactivity in the odontoblast soma and/or processes was detected for all proteins studied except α-ENa(+) C. The intensity of immunostaining was high for β-ENa(+) C and ASIC2, whereas it was low for ASIC1, ASIC3, γ-ENa(+) C, and TRPV4, being absent for α-ENa(+) C and ASIC4. These results suggest that human odontoblasts in situ express proteins related to mechanosensitive channels that probably participate in the mechanisms involved in teeth sensory transmission.

Brain-derived neurotrophic factor (BDNF) signaling through TrkB regulates different aspects of neuronal development, including survival, axonal and dendritic growth, and synapse formation. Despite recent advances in our understanding of the functional significance of BDNF and TrkB in the retina, the cell types in the retina that express BDNF and TrkB, and the variations in their levels of expression during development, remain poorly defined. The goal of the present study is to determine the age-dependent changes in the levels of expression and localization of BDNF and TrkB in the zebrafish retina. Zebrafish retinas from 10 days post-fertilization (dpf) to 180 dpf were used to perform PCR, Western blot and immunohistochemistry. Both BDNF and TrkB mRNAs, and BDNF and full-length TrkB proteins were detected at all ages sampled. The localization of these proteins in the retina was very similar at all time points studied. BDNF immunoreactivity was found in the outer nuclear layer, the outer plexiform layer and the inner plexiform layer, whereas TrkB immunoreactivity was observed in the inner plexiform layer and, to a lesser extent, in the ganglion cell layer. These results demonstrate that the pattern of expression of BDNF and TrkB in the retina of zebrafish remains unchanged during postembryonic development and adult life. Because TrkB expression in retina did not change with age, cells expressing TrkB may potentially be able to respond during the entire lifespan of zebrafish to BDNF either exogenously administered or endogenously produced, acting through paracrine mechanisms.

Pleiotrophin (PTN), a neurotrophic factor with important roles in survival and differentiation of dopaminergic neurons, is up-regulated in the nucleus accumbens after amphetamine administration suggesting that PTN could modulate amphetamine-induced pharmacological or neuroadaptative effects. To test this hypothesis, we have studied the effects of amphetamine administration in PTN genetically deficient (PTN ―/―) and wild type (WT, +/+) mice. In conditioning studies, we found that amphetamine induces conditioned place preference in both PTN ―/―) and WT (+/+) mice. When these mice were re-evaluated after a 5-day period without amphetamine administration, we found that WT (+/+) mice did not exhibit amphetamine-seeking behaviour, whereas, PTN ―/― mice still showed a robust drug-seeking behaviour. In immunohystochemistry studies, we found that amphetamine (10 mg/kg, four times, every 2 hours) causes a significant increase of glial fibrillary acidic protein positive cells in the striatum of amphetamine-treated PTN ―/― mice compared with WT mice 4 days after last administration of the drug, suggesting an enhanced amphetamine-induced astrocytosis in the absence of endogenous PTN. Interestingly we found in concomitant in vitro studies that PTN (3 μM) limits amphetamine (1 mM)-induced loss of viability of PC 12 cell cultures, effect that could be related to the ability of PTN to induce the phosphorylation of Akt and ERK1/2. To test this possibility, we used specific Akt and ERK1/2 inhibitors uncovering for the first time that PTN-induced protective effects against amphetamine-induced toxicity in PC12 cells are mediated by the ERK1/2 signalling pathway. The data suggest an important role of PTN to limit amphetamine-induced neurotoxic and rewarding effects.

Thymocytes and thymic stromal cells cross-talk in a bidirectional manner within the thymus, thus contributing to the generation of mature T-cells. The thymic stromal cells in the rat express the high- (TrkA, TrkB) and low-affinity (p75NTR) receptors for neurotrophins. In this study we analysed the regulation of TrkA, TrkB and p75NTR expression in the rat thymus by thymocytes. We induced thymocyte apoptosis by administration of corticoids in rats, and then analysed the expression and distribution of these receptors 1, 4 and 10 days later. Thymocyte death was assessed by the activation of caspase-3 in cells undergoing apoptosis. We observed massive thymocyte apoptosis 1 day after injection and, to a lesser extent, after 4 days, which was parallel with a reduction in the density of thymic epithelial cells normally expressing TrkA and p75NTR. Furthermore, TrkA expression was found in cortical thymic epithelial cells, which normally lack this receptor. The expression of TrkB was restricted to a subset of macrophage-dendritic cells, and remained unchanged with treatment. The normal pattern of neurotrophin receptor expression was almost completely restored by day 10. The results demonstrate that the expression of neurotrophin receptors by thymic epithelial cells, but not by macrophage-dendritic cells, is regulated by thymocytes.

This article reviews the distribution of S100 proteins in the human peripheral nervous system. The expression of S100 by peripheral glial cells seems to be a distinctive fact of these cells, independently of their localization and their ability to myelinate or not. S100 proteins expressing cells include satellite cells of sensory, sympathetic and enteric ganglia, supporting cells of the adrenal medulla, myelinating and non-myelinating Schwann cells in the nerve trunks, and the Schwann-related cells of sensory corpuscles. In addition, S100 proteins are expressed in peripheral neurons. Most of them express S100alpha protein, and a subpopulation of sensory neurons in dorsal root ganglia contains S100beta protein or S100alpha plus S100beta proteins.

A deeper understanding of biological materials and the design principles that govern them, combined with the enabling technology of 3D printing, has given rise to the idea of "building with biology." Using these materials and tools, bio-hybrid robots or bio-bots, which adaptively sense and respond to their environment, can be manufactured. Skeletal muscle bioactuators are developed to power these bio-bots, and an approach is presented to make them dynamically responsive to changing environmental loads and robustly resilient to induced damage. Specifically, since the predominant cause of skeletal muscle loss of function is mechanical damage, the underlying mechanisms of damage are investigated in vitro, and an in vivo inspired healing strategy is developed to counteract this damage. The protocol that is developed yields complete recovery of healthy tissue functionality within two days of damage, setting the stage for a more robust, resilient, and adaptive bioactuator technology than previously demonstrated. Understanding and exploiting the adaptive response behaviors inherent within biological systems in this manner is a crucial step forward in designing bio-hybrid machines that are broadly applicable to grand engineering challenges.

Null mutations of genes from the NGF family of NTs and their receptors (NTRs) lead to loss/reduction of specific neurons in sensory ganglia; conversely, cutaneous overexpression of NTs results in skin hyperinnervation and increase or no changes in the number of sensory neurons innervating the skin. These neuronal changes are paralleled with loss of specific types of sensory nerve formations in the skin. Therefore, mice carrying mutations in NT or NTR genes represent an ideal model to identify the neuronal dependence of each type of cutaneous sensory nerve ending from a concrete subtype of sensory neuron, since the development, maintenance, and structural integrity of sensory nerve formations depend upon sensory neurons. Results obtained from these mouse strains suggest that TrkA positive neurons are connected to intraepithelial nerve fibers and other sensory nerve formations depending from C and Adelta nerve fibers; the neurons expressing TrkB and responding to BDNF and NT-4 innervate Meissner corpuscles, a subpopulation of Merkell cells, some mechanoreceptors of the piloneural complex, and the Ruffini's corpuscles; finally, a subpopulation of neurons, which are responsive to NT-3, support postnatal survival of some intraepithelial nerve fibers and Merkel cells in addition to the muscle mechanoreceptors. On the other hand, changes in NTs and NTRs affect the structure of non-nervous structures of the skin and are at the basis of several cutaneous pathologies. This review is an update about the role of NTs and NTRs in the maintenance of normal cutaneous innervation and maintenance of skin integrity.