Neuroscience
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The event-related potential (ERP) mainly reflecting activation of the frontal lobe was measured during periodic floor oscillation, and changes in postural preparation and attention to the postural disturbance according to this adaptation were investigated. The experiment consisted of two tasks with eyes closed: adaptation to floor oscillation and finger flexion coinciding with the anterior and posterior reversals of oscillation. Subjects were 20 healthy young adults. ⋯ In the finger flexion task, a negative ERP peak was observed around each target point. This negative peak was related to the anticipatory attention directed to the reversal point and to motor preparation for finger flexion. It is conceivable that the increasing negative ERP in the adaptation task reflects the dynamics of motor preparation and attention mainly for the anterior reversal, where the negative ERP peak is closely related to anticipatory information processing of somatosensory stimuli arising around the time of the reversal.
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Reorganization of seizure networks during epileptogenesis involves cortico-subcortical and interhemispheric interactions. In the audiogenic kindling (AK) model of generalized tonic-clonic seizures, upstream seizure propagation along ascending brainstem-to-forebrain pathways determines progressive intensification of repeated sound-induced convulsions. Full-blown audiogenic seizures are bilaterally symmetric and their repetition results in bisynchronous recruiting the cortex in secondary epileptogenesis. ⋯ Among Wistar rats, cortical seizures developed more rarely in right-runners than in left-runners, suggesting enhanced resistance of the right hemisphere to epileptogenesis in rats of this strain. WAG/Rij rats with mixed (absence and audiogenic) epilepsy showed weak lateralization of early cortical seizures and no left-right difference in their incidence during AK. Present findings suggest (1) lateralized brainstem-to-forebrain seizure propagation and hemispheric difference in its facility in Wistar rats, (2) alterations of intra- and interhemispheric seizure propagation in WAG/Rij rats with genetic absence epilepsy.
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Traumatic brain injury (TBI) can dramatically increase levels of intracellular calcium (Ca²⁺). The association between Wnt5a/Frizzled-2 (wingless-type mouse mammary tumor virus integration site family member 5a/Fzd2) signaling and Ca²⁺ cellular homeostasis in lower vertebrates has been well documented. However, little is known about Wnt5a/Fzd2 signaling in mammalian nerve cells, or whether Ca²⁺ accumulation after TBI is mediated through this pathway. ⋯ Whereas, the in vivo blocking of Fzd2 signaling by hippocampal delivery of Stealth RNAi and Invivofectamine significantly suppressed the increased gene and protein expression of Wnt5a and Fzd2 induced by TBI by 1- to 3.5-fold (P<0.01) and also inhibited Ca²⁺ accumulation by 1.5-fold (P<0.01). These findings demonstrated that the Wnt5a/Fzd2 signaling pathway contributed to increasing intracellular Ca²⁺ in nerve cells under physiological and pathological conditions. Furthermore, our findings provide evidence that specifically expressed components of this signal pathway, such as Wnt5a and Fzd2, are potential therapeutic targets following brain trauma.
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Trigeminal ganglia neurons express the GABA(A) receptor subunit alpha 6 (Gabrα6) but the role of this particular subunit in orofacial hypersensitivity is unknown. In this report the function of Gabrα6 was tested by reducing its expression in the trigeminal ganglia and measuring the effect of this reduction on inflammatory temporomandibular joint (TMJ) hypersensitivity. Gabrα6 expression was reduced by infusing the trigeminal ganglia of male Sprague Dawley rats with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabrα6 siRNA) or no known gene (control siRNA). ⋯ Gabrα6 siRNA infusion reduced Gabrα6 gene expression by 30% and significantly lengthened meal duration in rats with TMJ inflammation. Gabrα6 siRNA infusion also significantly increased p-ERK expression in the trigeminal ganglia of rats with TMJ inflammation and increased electrical activity in the spinal cord of rats without TMJ inflammation. These results suggest that maintaining Gabrα6 expression was necessary to inhibit primary sensory afferents in the trigeminal pathway and reduce inflammatory orofacial nociception.
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Oligodendrocytes generate large amounts of myelin by extension of their cell membranes. Though lipid is the major component of myelin, detailed lipid metabolism in the maintenance of myelin is not understood. We reported previously that miR-32 might be involved in myelin maintenance (Shin et al., 2009). ⋯ Therefore, overexpression of SLC45A3 triggers neutral lipid accumulation. Interestingly, both overexpression and suppression of SLC45A3 reduces myelin protein expression in mature oligodendrocytes and alters oligodendrocyte morphology, indicating that tight regulation of SLC45A3 expression is necessary for the proper maintenance of myelin proteins and structure. Taken together, our data suggest that miR-32 and its downstream target SLC45A3 play important roles in myelin maintenance by modulating glucose and lipid metabolism and myelin protein expression in oligodendrocytes.