Neuroscience
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Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the transmission of nociceptive input in diabetic neuropathy. The aim of this study was to test whether intraganglionic (i.g.) injection of CaMKII inhibitors may alleviate pain-related behavior in diabetic rats. Diabetes was induced in Sprague-Dawley rats using 55 mg/kg streptozotocin intraperitoneally. ⋯ Attenuation of nociceptive behavior was accompanied with a corresponding decrease of CaMKII alpha expression in DRG neurons on the side of injection. A significant decrease of CaMKII alpha expression was seen in small- and medium-sized neurons. In conclusion, our study provides evidence that CaMKII inhibitors are potential pharmacological agents that should be further explored for treatment of diabetic neuropathy symptoms.
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α-Synuclein is the major component of Lewy bodies. α-Synuclein phosphorylated at Ser 129 (Phospho-α-Syn) is the most common synuclein modification observed in Parkinson's disease pathology and transgenic animal models. Polo-like kinase 2 (PLK2) was previously proposed as an important kinase in α-synuclein phosphorylation at Ser129. To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice. ⋯ Whereas BI 2536 reduced Phospho-α-Syn levels in WT mice, it did not further reduce the residual endogenous Phospho-α-Syn levels in PLK2 KO and Het mice, suggesting that a kinase other than PLK1-3 accounts for the remaining PLK inhibitor-resistant pool in the mouse brain. Moreover, PLK3 KO in mice had no effect on both Total- and Phospho-α-Syn brain levels. These results support a significant role for a PLK kinase in phosphorylating α-synuclein at Ser129 in the brain, and suggest that PLK2 is responsible for this activity under physiological conditions.
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Verbal insight problem solving means to break mental sets, to select the novel semantic information and to form novel, task-related associations. Although previous studies have identified the brain regions associated with these key processes, the interaction among these regions during insight is still unclear. ⋯ Compared with noninsight solution, insight solution had a stronger functional connectivity between the inferior frontal gyrus and middle temporal gyrus in the right hemisphere. Our study reveals the neural pathway of information processing during verbal insight problem solving, and supports the right-hemisphere advantage theory of insight.
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Tinnitus is a bothersome phantom sound percept and its neural correlates are not yet disentangled. Previously published papers, using [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), have suggested an increased metabolism in the left primary auditory cortex in tinnitus patients. This unilateral hyperactivity has been used as a target in localized treatments such as transcranial magnetic stimulation. ⋯ Nevertheless, the activity in the left primary auditory cortex was higher than in the right primary auditory cortex, but this asymmetry was present in both tinnitus patients and control subjects. In contrast, the lateralization in secondary auditory cortex was opposite, with higher activation in the right hemisphere. These data show that hemisphere asymmetries in the metabolic resting activity of the auditory cortex are present, but these are not associated with tinnitus and are a normal characteristic of the normal brain.
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Under normal conditions, the acoustic pitch percept of a pure tone is determined mainly by the tonotopic place of the stimulation along the cochlea. Unlike acoustic stimulation, electric stimulation of a cochlear implant (CI) allows for the direct manipulation of the place of stimulation in human subjects. CI sound processors analyze the range of frequencies needed for speech perception and allocate portions of this range to the small number of electrodes distributed in the cochlea. ⋯ This trend was particularly apparent when the allocations of stimulus frequencies to electrodes were changed over time, with pitch changes even reversing direction in some subjects. These findings show that pitch plasticity can occur more rapidly and on a greater scale in the mature auditory system than previously thought possible. Overall, the results suggest that the adult auditory system can impose perceptual order on disordered arrays of inputs.