No abstract

This review considers pathophysiological mechanisms of posture-gait disturbances in Parkinson's disease (PD). Clinical studies have shown that posture-gait disturbance attributes to the dysfunction of the whole neuraxis in addition to the musculoskeletal system. The cerebral cortex, basal ganglia (BG), cerebellum, brainstem, and spinal cord temporally and spatially integrate and coordinate multisensory feedback and efferent copies of the motor command. Therefore, the extensive repertoire of voluntary movements can be coupled with anticipatory and reactive postural adjustments to provide the framework for supporting and stabilizing the goal-directed gait activity. Redundancies in the system allow adaptation and compensation through reward-oriented and error-based learning processes implemented through the BG and cerebellar pathways, respectively.However, the impairment of these systems in PD may considerably compromise the capacity to adapt and lead to maladaptive changes impairing posture-gait control. When these impairments occur, the risk of falls can significantly increase, and interventions are required to reduce morbidity. The damage in dopamine (DA) neurons is the primary cause of PD. Insufficient DA supply in the striatum disturbs the operation of intrinsic networks in the BG. This also pathologically increases GABAergic BG output to the cerebral cortex and brainstem, resulting in functional disconnection of other structures from the BG. The disconnection makes PD patients disable to achieve habitually acquired automatized gait control. Moreover, Lewy body degeneration in most brain areas, particularly in cholinergic and other monoaminergic systems vulnerable to neurodegeneration, further disturbs posture-gait control and alters non-motor symptoms of PD.

Abstract. The present study was undertaken to investigate the function of protease-activated receptor (PAR) in endometriotic lesions using a mouse model of endometriosis. Unilateral ovariectomy (uOVX) was performed on female nude mice followed by intraperitoneal transplantation of a suspension mixture of immortalized human endometrial epithelial cells (EM-1) and stromal cells (EtsT-499). Endometriosis-like lesions were observed mostly around the dissection site after transplantation. The expression of interleukin (IL)-6 and cyclooxygenase-2 in the lesions was enhanced in uOVX mice compared to non-uOVX animals. In non-uOVX mice, IL-6 mRNA levels were higher in lesions formed with cells that were pretreated with PAR1/2 agonists (thrombin, 10 U/ml and PAR2-activating peptide, 30 μM) compared to untreated, intact cells. Peritoneal IL-6 concentrations were also increased in the PAR1/2 agonists-treated group. IL-6 expression induced by PAR activation was blocked by the treatment of cells with serine protease inhibitors. In cultured endometrial cells, simultaneous treatment with PAR1 and PAR2 agonists significantly increased the expression of IL-6. These results suggest that peritoneal bleeding may accelerate IL-6 expression in endometriotic lesions in part through the activation of PAR.

No abstract

Postural control precedes the goal-directed movement to maintain body equilibrium during the action. Because the environment continuously changes due to one’s activity, postural control requires a higher-order brain function that predicts the interaction between the body and the environment. Here, we tried to elucidate to what extent such a preceding postural control (PPC) predictively offered a posture that ensured the entire process of the goal-directed movement before starting the action. For this purpose, we employed three cats, which we trained to maintain a four-leg standing posture on force transducers to reach the target by either forelimb. Each cat performed the task under nine target locations in front with different directions and distances. As an index of posture, we employed the center of pressure (CVP) and examined CVP positions when the cat started postural alteration, began to lift its paw, and reached the target. After gazing at the target, each cat started PPC where postural alteration was accompanied by a 20–35 mm CVP shift to the opposite side of the forelimb to be lifted. Then, the cat lifted its paw at the predicted CVP position and reached the forelimb to the target with a CVP shift of only several mm. Moreover, each cat had an optimal target location where the relationship between the cat and target minimized the difference in the CVP positions between the predicted and the final. In this condition, more than 80% of the predicted CVP positions matched the final CVP positions, and the time requiring the reaching movement was the shortest. By contrast, the forelimb reaching movement required a greater CVP shift and longer time when the target was far from the cat. In addition, the time during forelimb reaching showed a negative correlation with the speed of the CVP shift during the PPC. These results suggest that the visuospatial information, such as the body-environment interaction, contributes to the motor programming of the PPC. We conclude that the PPC ensures postural stability throughout the action to optimize the subsequent goal-directed movements. Impairments in these processes may disturb postural stability during movements, resulting in falling.