Neuroscience
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In the CNS, juxtanodin (JN) is an actin-binding oligodendroglial protein that functions to promote differentiation of the host cells during postnatal development. In other tissues, JN expression and function remain unknown. We surveyed rat peripheral nerve, skeletal muscle and various epithelial tissues using immunoblotting and light-microscopic immunohistochemistry, and found prominent JN expression only in the olfactory epithelium (OE). ⋯ Distribution of JN in the OE differed from that of class III beta-tubulin or nestin, but partially overlapped with a zone of intense F-actin staining near the OE mucous surface. Together these results identify JN as a marker protein for OE sustentacular cells, and support the glia-like nature of OE sustentacular cells. Functionally, JN in the OE might help in the molecular specialization of distinct compartments of olfactory receptor neurons (ORNs), in the interaction of sustentacular cells with ORNs, and/or in maturation/maintenance of sustentacular cells.
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The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. ⋯ Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.
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Fas-associated protein with death domain (FADD) is a multifunctional protein that can induce both apoptotic and non-apoptotic actions. Recently, FADD was found downregulated in the prefrontal cortex of opiate abusers, which suggested an attenuation of Fas death signals in human addicts. Phosphorylation of FADD (Ser194) has been reported to regulate its non-apoptotic activity, which might include the induction of neuroplastic effects in the brain. ⋯ Similarly, the signaling pathway mediated by p-phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) protein and its phosphorylating kinase p-Akt1 was also downregulated in cortical homogenate (43% and 41%, respectively) and cytosolic preparations of chronic opiate addicts. The results indicate that opiate addiction in humans is associated with an altered balance between p-Ser194 FADD (increased) and total FADD (decreased) in brain, which may favor its neuroplastic actions. The interaction between p-FADD (upregulated) and neuronal pathways (downregulated) could play a relevant role in mediating specific forms of structural and behavioral neuroplasticity.
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Evidence from developmental and regeneration studies of the cochlea and other tissues gives reason to hypothesize a role for nonneural cells in the growth and regeneration of cochlear spiral ganglion nerve fibers. We examined the spontaneous associations of regrowing neurites and nonneural cells in mixed cultures of dissociated newborn mouse spiral ganglia. After 7 days in vitro, nonneural cells formed a confluent layer in the culture well. ⋯ Immunolabeling of fixed cochleas from neonatal mice localized Sox10, P75 and connexin29, to peripheral nerve bundles. The observed expressions of protein markers and the bipolar, spindle shape of the neurite-associated cells indicate that they are derived in vitro from the original Schwann or satellite cells in the ganglion or spiral lamina. The spontaneous and preferential association of neurites in culture with mitotic Schwann cells highlights the potential contribution neurite-Schwann cell interactions may have in promoting the growth and regrowth of damaged spiral ganglion neurons in the cochlea.
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Lumbar intrathecal injection of neuropeptide Y (NPY) is antinociceptive, particularly in models of nerve injury and inflammation. Intrathecal NPY does not alter nociception in mice null for the Y1 neuropeptide Y receptor (Y1R) and these mice show enhanced nocifensive reflex responses to aversive thermal, mechanical, visceral and chemical stimuli. Y1R and NPY receptor type 2 (Y2R) are present in the spinal dorsal horn presynaptically on primary afferent, and possibly interneuron terminals, but only Y1R is found postsynaptically on dorsal horn neurons. ⋯ First hind-paw response latencies to high intensity phasic stimulation at 52 degrees C were unaffected. NPY-sap also reduced formalin-induced nocifensive behaviors during both interphase and phase II. These data demonstrate that selective destruction of Y1R-expressing superficial dorsal horn neurons, probably excitatory interneurons and/or projection neurons, reduces nocifensive reflex responses, particularly to activation of C nociceptors, and suggest a possible role for Y1R-expressing dorsal horn neurons in pain.