Neuroscience
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Alzheimer's disease (AD) is associated with beta-amyloid deposition, glial activation, and increased levels of the cytokines, as well as cholinergic dysfunction. Liver X receptor (LXR) has been found to inhibit the expression of pro-inflammatory genes. However, the effects of LXR activation on inflammatory response and on cholinergic system in AD are not yet clear. ⋯ LXR activation and nuclear factor kappa B (NF-κB) inhibitor PDTC both attenuated Aβ(25-35) induction of NF-κB activation. These results suggest that LXR agonists suppress the production of pro-inflammatory molecules, at least in part, by modulating NF-κB-signaling pathway. Collectively, these studies suggest that LXR agonists may have therapeutic significance in AD.
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Tremor is one of the cardinal symptoms of Parkinson's disease. Up to now, however, its pathophysiology remains poorly understood. Previously, oscillatory coupling at tremor frequency between the subthalamic nucleus und affected muscles was shown. ⋯ Furthermore, the clinical effective stimulation site coincided with the location of most input causalities from the periphery in seven out of eight tremor-dominant patients. The data suggest that, although tremor activity in tremor-dominant and akinetic-rigid Parkinson's disease patients was clinically similar, statistical causality between tremor electromyogram (EMG) and the subthalamic nucleus was fundamentally different. Therefore, we hypothesize different pathophysiological mechanisms to underlie the generation of tremor in the two subtypes of Parkinson's disease.
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Lead intoxication has been suggested as a high risk factor for the development of Parkinson disease. However, its impact on motor and nonmotor functions and the mechanism by which it can be involved in the disease are still unclear. In the present study, we studied the effects of lead intoxication on the following: (1) locomotor activity using an open field actimeter and motor coordination using the rotarod test, (2) anxiety behavior using the elevated plus maze, (3) "depression-like" behavior using sucrose preference test, and (4) subthalamic nucleus (STN) neuronal activity using extracellular single unit recordings. ⋯ The electrophysiological results show that lead altered the discharge pattern of STN neurons with an increase in the number of bursting and irregular cells without affecting the firing rate. Moreover, lead intoxication resulted in a decrease of tissue noradrenaline content without any change in the levels of dopamine and serotonin. Together, these results show for the first time that lead intoxication resulted in motor and nonmotor behavioral changes paralleled by noradrenaline depletion and changes in the firing activity of STN neurons, providing evidence consistent with the induction of atypical parkinsonian-like deficits.
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This is a study on associated postural activities during the anticipatory segments of a multijoint movement. Several previous studies have shown that they are task dependant. The previous studies, however, have mostly been limited in demonstrating the presence of modulation for one task condition, that is, one aspect such as the distance of the target or the direction of reaching. ⋯ This suggests that more specific modulations for the movement at hand take place through activation, whereas the deactivation is more general. The study introduces a new method for investigating adaptations in motor control. It also sheds new light on the quantity and quality of information available in the feedforward segments of a voluntary multijoint motor activity.
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Previous studies on handedness have often reported functional asymmetries in corticomotor excitability (CME) associated with voluntary movement. Recently, we have shown that the degree of post-exercise corticomotor depression (PED) and increase in short-interval cortical inhibition (SICI) after a repetitive finger movement task was less when the task was performed at a maximal voluntary rate (MVR) than when it was performed at a submaximal sustainable rate (SR). In the current study, we have compared the time course of PED and SICI in the dominant (DOM) and nondominant (NDOM) hands after an MVR and SR finger movement task to determine the influence of hand dominance and task demand. ⋯ We find that the least demanding task, one that involved index finger movement of the DOM hand at SR, was associated with the greatest change in PED and SICI from baseline (63.6±5.7% and 79±2%, P<0.001, PED and SICI, respectively), whereas the most demanding task (MVR of the NDOM hand) was associated with the least change from baseline (PED: 88.1±3.6%, SICI: 103±2%; P<0.001). Our findings indicate that the changes in CME and inhibition associated with repetitive finger movement are influenced both by handedness and the degree of demand of the motor task and are inversely related to task demand, being smallest for an MVR task of the NDOM hand and greatest for an SR task of the DOM hand. The findings provide additional evidence for differences in neuronal processing between the dominant and nondominant hemispheres in motor control.