Neuroscience
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Synaptotagmin (syt) I is a Ca(2+) sensor that has been thought to trigger all vesicle secretion with similar mechanisms. However, given the calcium and stimulation requirements of small clear, and large dense core vesicles, we hypothesized that syt I expression differentially regulates vesicle release. Therefore, in this study, we generated multiple stable cell lines of PC12 cells that each had a different and stable level of syt I expression. ⋯ We used an immunoassay to measure NPY release and found that NPY release was abolished in cells that had abolished syt I expression, but cell lines that expressed 50-60% of control levels of syt I exhibited NPY release levels comparable to release of NPY from control cells. Furthermore, the vesicle fusion pore exhibited a reduced open duration when syt I was abolished, but a longer open duration time for 50% syt I expression than control cells. Therefore, vesicles have a threshold for syt I that is required to control opening of the fusion pore, expansion, and full fusion to release large dense core proteins, but not for full fusion of the small molecules like NE.
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Hydrogen sulfide (H(2)S), an endogenous gasotransmitter, modulates various biological functions, including nociception. It is known that H(2)S causes neurogenic inflammation and elicits hyperalgesia. Here we show that H(2)S activates mouse transient receptor potential ankyrin 1 (TRPA1) channels and elicits acute pain, using TRPA1-gene deficient mice (TRPA1(-/-)) and heterologous expression system. ⋯ The [Ca(2+)](i) responses to H(2)S in sensory neurons and in heterologously expressed channels, and pain-related behavior induced by H(2)S were enhanced under acidic conditions. These results suggest that H(2)S functions as a nociceptive messenger through the activation of TRPA1 channels. TRPA1 may be a therapeutic target for H(2)S-related algesic action, especially under inflammatory conditions.
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Transcranial magnetic stimulation (TMS) studies have shown that the motor system is facilitated when we imagine performing motor actions. However, it is not clear whether the individual's motor system modulates bilaterally and selectively for task parameters, such as movement direction and amplitude. To investigate this issue, we applied single-pulse TMS over the left and right primary motor cortex (M1) of healthy subjects, who had to imagine grasping and rotating a clock hour hand, having a starting position at noon, towards four different times: 2, 5, 7 and 10 o'clock. ⋯ Results showed that during motor imagery a mirroring pattern was present between the right and the left motor cortices, showing selective activation of the hand-intrinsic muscles spatially close to the direction of the imagined movement. Overall a higher activation for large and a lower activation for small rotation angle were found, but no selective muscle activity was present within the hand-intrinsic muscles for this parameter. Following these results we propose that during action imagination an internally coded covariance between movement parameters is present with a muscle-specific activation for movement direction.
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Our previous studies have demonstrated that application of inflammatory irritant mustard oil (MO) to the tooth pulp induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. ⋯ However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (analysis of variance (ANOVA), p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial inflammatory pain states.
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Comparative Study
The differential profiles of withdrawal symptoms induced by morphine and beta-endorphin administered intracerebroventricularly in mice.
In the present study, withdrawal symptoms induced by morphine or β-endorphin administered intracerebroventricularly (i.c.v.) were compared in ICR mice. Naloxone (10mg/kg) was post-treated intraperitoneally (i.p.) 3h after either a single or repeated (1 time/day for 3 days) i.c.v. injections with opioids. Withdrawal symptoms such as jumping frequency, diarrhea, weight loss, rearing, penile licking and paw tremor were observed for 30 min immediately after naloxone treatment. ⋯ In contrast with the findings in morphine-treated group, only pCaMK-IIα expression was decreased by naloxone treatment in repeatedly administered β-endorphin group. Our results suggest that profiles of the withdrawal symptoms induced by morphine and β-endorphin administered supraspinally appear to be differentially regulated. The pCaMK-IIα and the c-FOS protein expression may play important roles for the regulation of naloxone-precipitated withdrawal symptoms such as jumping, diarrhea, weight loss, rearing, penile licking and paw tremor induced by morphine-treated group, whereas the phosphorylation of hypothalamic pCaMK-IIα appears to be involved only in the regulation of naloxone-precipitated withdrawal symptoms such as diarrhea, weight loss and rearing in β-endorphin-treated group.