Neuroscience
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Widespread pain and anxiety are commonly reported in cancer patients. We hypothesize that cancer is accompanied by attenuation of endogenous opioid-mediated inhibition, which subsequently causes widespread pain and anxiety. To test this hypothesis we used a mouse model of oral squamous cell carcinoma (SCC) in the tongue. ⋯ Moreover, opioid receptor agonists did not yield a statistically significant effect on behaviors measured in the open field and elevated maze in cancer mice. Lastly, we used an acute cancer pain model (injection of cancer supernatant into the mouse tongue) to test whether adaptation to chronic pain is responsible for the absence of greater anxiety-like behavior in cancer mice. No changes in anxiety-like behavior were observed in mice with acute cancer pain.
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The innate immune responses of brain to vascular occlusion are primarily orchestrated by activated microglia. However, the roles of microglia in inflammatory responses to brain ischemic injuries are controversial. Here, we report a new mechanism by which microglia confer protective effects on ischemic neuronal cells. ⋯ Furthermore, blocking BAFF-BAFFR ligation with TACI-Ig abrogated these therapeutic benefits. Taken together, these results indicate that the BAFF-BAFFR ligation bridged between microglia and neurons could play a critical neuroprotective role in I/R injury. Thus, augmenting BAFF-BAFFR signaling might represent a potential target for clinical stroke therapy.
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Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. ⋯ We also injected MSG to crv4 mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in crv4 mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration.
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Prolonged use/abuse of opioid agonists leads to development of severe dependence to these drugs. Orexin-A has a crucial role in development of morphine dependence. The locus coeruleus (LC) is implicated in the expression of morphine withdrawal signs. ⋯ Chronic morphine injection induced morphine dependence in LC neurons which was revealed as a significant increase in LC neuronal firing rate in response to naloxone. The results of this study indicated that SB-334867 administration prior to each morphine injection prevents naloxone-elicited neuronal activation within the LC. In addition, naloxone injection enhanced the cAMP concentration in LC neurons of morphine-dependent animals and this effect was significantly reduced by OX1R blockade.
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Patients sometimes complain that non-vital teeth after root canal treatment (RCT) are paresthesia compared with vital teeth, and previous psychological studies on the tactile sensibility of non-vital teeth remained controversial. In the present study, intrinsic signal optical imaging, which served as an objective tool, was employed to compare the cortex response characteristics following forces applied to the cat non-vital and vital canines. Based on the evoked cortical responses, the response threshold, signal strength, spatial pattern, temporal dynamics and the preference of force direction, they were not significantly different between vital and non-vital canines. It seemed that the tactile sensibility of vital and non-vital teeth was comparable at the cortical response level, and pulpal receptors were not concerned in tactile function.