Fibroblast mitochondria in idiopathic Parkinson's disease display morphological changes and enhanced resistance to depolarization.

Mitochondrial dysfunction is a hallmark in idiopathic Parkinson's disease (IPD). Here, we established screenable phenotypes of mitochondrial morphology and function in primary fibroblasts derived from patients with IPD. Upper arm punch skin biopsy was performed in 41 patients with mid-stage IPD and 21 age-matched healthy controls. At the single-cell level, the basal mitochondrial membrane potential (Ψm) was higher in patients with IPD than in controls. Similarly, under carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) stress, the remaining Ψm was increased in patients with IPD. Analysis of mitochondrial morphometric parameters revealed significantly decreased mitochondrial connectivity in patients with IPD, with 9 of 14 morphometric mitochondrial parameters differing from those in controls. Significant morphometric mitochondrial changes included the node degree, mean volume, skeleton size, perimeter, form factor, node count, erosion body count, endpoints, and mitochondria count (all P-values < 0.05). These functional data reveal that resistance to depolarization was increased by treatment with the protonophore FCCP in patients with IPD, whereas morphometric data revealed decreased mitochondrial connectivity and increased mitochondrial fragmentation.

A dynamic model of a device with a parallel-serial structure to support the human lower limb.

BACKGROUND: Support systems designed for human lower limbs are usually characterized by a serial kinematic structure taking into account only one lower limb. To overcome the mobility range limitations, a new structure of the exoskeleton is proposed in this paper. OBJECTIVE: The design process of the dynamic model for the support structure characterized by a parallel-serial mechanism is presented in the paper. The structure works as an exoskeleton and is designed to assist motion of the human lower limb in the process of rehabilitation. METHODS: The structure of the support model was divided into linear (executive system) and nonlinear (the mechanical skeleton of the system) parts. The model of the executive system was designed and its parameters were estimated in the course of tests on a laboratory stand, as well as identification procedures. The nonlinear model was expressed by mathematical equations. The characteristic coefficients in the equation were determined based on a 3d CAD model. RESULTS: To analyze the behavior of the mechanism, a simulation of dynamic responses was compared with experimental results for a real system consisting of a mechatronic device, actuator drivers, a controller, and programmed software. CONCLUSIONS: The proposed new structure enables an increase of the range of rotation angles and can be fitted to an individual person. The derived model is in the analytical form and can also be easily adopted to the different versions of the exoskeleton and used in the design of control systems.

Enteric neurons from Parkinson's disease patients display ex vivo aberrations in mitochondrial structure.

Based on autopsy material mitochondrial dysfunction has been proposed being part of the pathophysiological cascade of Parkinson's disease (PD). However, in living patients, evidence for such dysfunction is scarce. As the disease presumably starts at the enteric level, we studied ganglionic and mitochondrial morphometrics of enteric neurons. We compared 65 ganglia from 11 PD patients without intestinal symptoms and 41 ganglia from 4 age-matched control subjects. We found that colon ganglia from PD patients had smaller volume, contained significantly more mitochondria per ganglion volume, and displayed a higher total mitochondrial mass relative to controls. This suggests involvement of mitochondrial dysfunction in PD at the enteric level. Moreover, in PD patients the mean mitochondrial volume declined in parallel with motor performance. Ganglionic shrinking was evident in the right but not in the left colon. In contrast, mitochondrial changes prevailed in the left colon suggesting that a compensatory increase in mitochondrial mass might counterbalance mitochondrial dysfunction in the left colon but not in the right colon. Reduction in ganglia volume and combined mitochondrial morphometrics had both predictive power to discriminate between PD patients and control subjects, suggesting that both parameters could be used for early discrimination between PD patients and healthy individuals.