Neuroscience
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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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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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Neuroglobin (Ngb) is a new member of the globin family and a novel endogenous neuroprotective molecule, but its neuroprotective mechanisms remain largely undefined. Previous studies suggest Ngb is both physically and functionally related to mitochondria, however without direct evidence. Our recent discovery has shown that Ngb can physically interact with a number of mitochondrial proteins. ⋯ Complementary approaches including confocal imaging and immuno-electron microscopy confirmed Ngb distribution in mitochondria under both basal-resting condition and OGD. Inhibitors of mitochondria permeability transition pore (mPTP) and Voltage-Dependent Anion Channel (VDAC) blocked OGD-induced increase of mitochondrial Ngb level, demonstrating a possible role of mPTP in Ngb's mitochondrial translocation. We further found that Ngb overexpression-conferred neuroprotection was correlated with increased mitochondrial Ngb level, suggesting the mitochondria distribution of Ngb is clearly associated with and may contribute to Ngb's neuroprotection.
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Anhedonia is a core symptom of clinical depression. Two brain neuropeptides that have been implicated in anhedonia symptomology in preclinical depression models are dynorphin and orexin; which are concentrated along lateral hypothalamic dopamine reward pathways. These affect regulating neuropeptides modulate each other's function, implicating an interactive dysfunction between them in anhedonia symptomology. ⋯ But orexin was reduced in the VTA and mPFC. Also, dynorphin and orexin were both diminished in the hypothalamus which is noteworthy since nearly all hypothalamic orexin cells co-express dynorphin. These findings suggest that orexin and dynorphin function may be imbalanced between the hypothalamus and mesocortical dopaminergic brain regions in depression.