Neuroscience
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Medullary dorsal horn (MDH), the homolog of spinal dorsal horn, plays essential roles in processing of nociceptive signals from orofacial region toward higher centers, such as the ventral posteromedial thalamic nucleus (VPM) and parafascicular thalamic nucleus (Pf), which belong to the sensory-discriminative and affective aspects of pain transmission systems at the thalamic level, respectively. In the present study, in order to provide morphological evidence for whether neurons in the MDH send collateral projections to the VPM and Pf, a retrograde double tracing method combined with immunofluorescence staining for substance P (SP), SP receptor (SPR) and Fos protein was used. Fluoro-gold (FG) was injected into the VPM and the tetramethylrhodamine-dextran (TMR) was injected into the Pf. ⋯ It was also found that some of the FG/TMR double-labeled neurons within lamina I expressed SPR and were in close contact with SP-immunoreactive (SP-ir) terminals. After formalin injection into the orofacial region, 41.4% and 34.3% of the FG/TMR double-labeled neurons expressed Fos protein in laminae I and III, respectively. The present results provided morphological evidence for that some SPR-expressing neurons within the MDH send collateral projections to both VPM and Pf and might be involved in sensory-discriminative and affective aspects of acute orofacial nociceptive information transmission.
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Acute cutaneous exposure to allergen often leads to itch, but seldom pain. The effect of mast cell activation on cutaneous C-fibers was studied using innervated isolated mouse skin preparation that allows for intra-arterial delivery of chemicals to the nerve terminals in the skin. Allergen (ovalbumin) injection into the isolated skin of actively sensitized mice strongly stimulated chloroquine (CQ)-sensitive C-fibers (also referred to as "itch" nerves); on the other hand, CQ-insensitive C-fibers were activated only modestly, if at all. ⋯ Ovalbumin also strongly activated itch C-fibers in skin isolated from Mrgpr-cluster Δ-/- mice. When pyrilamine was studied in the Mrgpr-cluster Δ-/- mice thereby eliminating the influence of both histamine H1 and Mrgpr receptors (MrgprA3 and C11 are selectively expressed by itch nerves), the ovalbumin response was very nearly eliminated. The data indicate that the acute activation of itch C-fibers in mouse skin is largely secondary to the combined effect of activation of histamine H1 and Mrpgr receptors.
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Neuropeptide Y is a peptide neuromodulator with protective roles including anxiolytic and antidepressant-like effects in animal models of depression and post-traumatic stress disorder. The lateral habenula (LHb) is a brain region that encodes aversive information and is closely related with mood disorders. Although LHb neurons express NPY receptors, the physiological roles of NPY in this region remain uninvestigated. ⋯ Inhibitory transmission remained unchanged by NPY application in a subset of neurons but was reduced in the majority of LHb neurons recorded. The overall outcome of NPY application was a decrease in the spontaneous firing rate of the LHb, leading to hypoactivation of the LHb. Our observations indicate that although NPY has divergent effects on excitatory and inhibitory transmission, NPY receptor activation decreases LHb activity, suggesting that the LHb may partly mediate the protective roles of NPY in the central nervous system.
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Alzheimer's disease (AD) is the neurodegenerative disorder with no cure. Recent studies suggest that dysregulated postsynaptic store-operated calcium entry (nSOCE) may underlie mushroom spine loss that is related to AD pathology. ⋯ We further established that nSOCE antagonist EVP4593 decreases PSEN1ΔE9-mediated nSOCE upregulation and rescues mushroom spines in PSEN1ΔE9-expressing neurons. Obtained results further highlight the connection between dysregulation of endoplasmic reticulum calcium signaling and synaptic loss in AD and suggest that calcium signaling modulators may have a therapeutic value for treatment of memory loss in AD.
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Sestrin2 (Sesn2) is a stress response protein which expresses neuroprotective characteristics in some neurodegenerative disorders. However, the impact of Sesn2 on the clinical outcome of stroke is unclear. The nuclear factor-erythroid 2 related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway is a key factor in angiogenesis, which aids in attenuating cerebral ischemia damage. ⋯ While Sesn2, Nrf2, HO-1, and VEGF were significantly increased following cerebral ischemia, overexpression of Sesn2 further increased their expression. After silencing Nrf2, the opposite effect was observed. These results imply that Sestrin2 may activate the Nrf2 / HO-1 pathway, leading to enhanced angiogenesis following photothrombotic cerebral ischemia.