Bmc Neurosci
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Recent work has shown that the chaperone resistant to inhibitors of acetylcholinesterase (RIC-3) is critical for the folding, maturation and functional expression of a variety of neuronal nicotinic acetylcholine receptors. α7 nicotinic receptors can only assemble and functionally express in select lines of cells, provided that RIC-3 is present. In contrast, α4β2 nicotinic receptors can functionally express in many cell lines even without the presence of RIC-3. Depending on the cell line, RIC-3 has differential effects on α4β2 receptor function - enhancement in mammalian cells but inhibition in Xenopus oocytes. Other differences between the two receptor types include nicotine-induced upregulation. When expressed in cell lines, α4β2 receptors readily and robustly upregulate with chronic nicotine exposure. However, α7 nicotinic receptors appear more resistant and require higher concentrations of nicotine to induce upregulation. Could the coexpression of RIC-3 modulate the extent of nicotine-induced upregulation not only for α7 receptors but also α4β2 receptors? We compared and contrasted the effects of RIC-3 on assembly, trafficking, protein expression and nicotine-induced upregulation on both α7 and α4β2 receptors using fluorescent protein tagged nicotinic receptors and Förster resonance energy transfer (FRET) microscopy imaging. ⋯ These results provide interesting novel data that RIC-3 differentially regulates assembly and expression of different nicotinic receptor subunits. These results also show that nicotine-mediated upregulation of α4β2 receptors can be dynamically regulated by the presence of the chaperone, RIC-3. This could explain a novel mechanism why high affinity α4β2 receptors are upregulated in specific neuronal subtypes in the brain and not others.
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Randomized Controlled Trial
Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex.
Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test. ⋯ These results indicate that tDCS induced behavioural changes in the non-dominant hand as a consequence of mechanisms associated with use-dependant cortical plasticity that is independent of the electrode arrangement.
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The nociceptive withdrawal reflex (NWR) has been proven to be a valuable tool in the objective assessment of central hyperexcitability in the nociceptive system at spinal level that is present in some chronic pain disorders, particularly chronic low back and neck pain. However, most of the studies on objective assessment of central hyperexcitability focus on population differences between patients and healthy individuals and do not provide tools for individual assessment. In this study, a prediction model was developed to objectively assess central hyperexcitability in individuals. The method is based on statistical properties of the EMG signals associated with the nociceptive withdrawal reflex. The model also supports individualized assessment of patients, including an estimation of the confidence of the predicted result. ⋯ A prediction model was proposed and successfully tested as a new approach for objective assessment of central hyperexcitability in the nociceptive system, based on statistical properties of EMG signals recorded after eliciting the NWR. Therefore, the present statistical prediction model constitutes a first step towards potential applications in clinical practice.
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The nociceptive withdrawal reflex (NWR) is a polysynaptic spinal reflex that induces complex muscle synergies to withdraw a limb from a potential noxious stimulus. Several studies indicate that assessment of the NWR is a valuable objective tool in relation to investigation of various pain conditions. However, existing methodologies for NWR assessment evaluate standard surface electromyography (sEMG) measured over just one muscle and do not consider the possible interference of crosstalk originating from adjacent active muscles. The present study had two aims: firstly, to investigate to which extent the presence of crosstalk may affect NWR detection using a standardized scoring criterion (interval peak z-score) that has been validated without taking crosstalk into consideration. Secondly, to investigate whether estimation of muscle fiber conduction velocity can help identifying the propagating and non-propagating nature of genuine reflexes and crosstalk respectively, thus allowing a more valid assessment of the NWR. ⋯ This study investigated the negative effect of electrical crosstalk during reflex detection and revealed that the use of a previously validated scoring criterion may result in poor specificity due to crosstalk. The excellent performance of the developed methodology in the presence of crosstalk shows that assessment of muscle fiber conduction velocity allows reliable detection of EMG crosstalk during reflex detection.
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Randomized Controlled Trial
Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-α.
Tumor necrosis factor-alpha (TNF-α) is elevated early in injured brain after traumatic brain injury (TBI), in humans and in animals. Etanercept (a TNF-α antagonist with anti-inflammatory effects) attenuates TBI in rats by reducing both microglial and astrocytic activation and increased serum levels of TNF-α. However, it is not known whether etanercept improves outcomes of TBI by attenuating microglia-associated, astrocytes-associated, and/or neurons-associated TNF-α expression in ischemic brain. A well clinically relevant rat model, where a lateral fluid percussion is combined with systemic administration of etanercept immediately after TBI, was used. The neurological severity score and motor function was measured on all rats preinjury and on day 3 after etanercept administration. At the same time, the neuronal and glial production of TNF-α was measured by Immunofluorescence staining. In addition, TNFα contents of ischemic cerebral homogenates was measured using commercial enzyme-linked immunosorbent assay kits. ⋯ This finding indicates that early microglia overproduction of TNF-α in the injured brain region after TBI contributes to cerebral ischemia and neurological motor deficits, which can be attenuated by etanercept therapy. Studies in this model could provide insight into the mechanisms underlying neurological motor disturbance in brain-injured patients.