The impact of ATP-sensitive potassium channel modulation on mitochondria in a Parkinson's disease model using SH-SY5Y cells depends on their differentiation state.

Inward rectifying potassium channels sensitive to ATP levels (KATP) have been the subject of investigation for several decades. Modulators of KATP channels are well-established treatments for metabolic as well as cardiovascular diseases. Experimental studies have also shown the potential of KATP modulation in neurodegenerative disorders. However, to date, data regarding the effects of KATP antagonists/agonists in experiments related to neurodegeneration remain inconsistent. The main source of confusion in evaluating available data seems to be the choice of experimental models. The present study aims to provide a comprehensive understanding of the effects of both opening and blocking KATP channels in two forms of SH-SY5Y cells. Our results offer valuable insights into the significance of metabolic differences between differentiated and non-differentiated SH-SY5Y cells, particularly in the context of glibenclamide and diazoxide effects under normal conditions and during the initiation of pathological events simulating Parkinson's disease in vitro. We emphasize the analysis of mitochondrial functions and changes in mitochondrial network morphology. The heightened protein expression of KATP channels identified in non-differentiated SH-SY5Y cells seems to be a platform for a more significant impact of KATP modulators in this cell type. The efficiency of rotenone treatment in inducing morphological changes in the mitochondrial network depends on the differentiation status of SH-SY5Y cells.

Vulnerability of subcellular structures to pathogenesis induced by rotenone in SH-SY5Y cells.

Numerous pathological changes of subcellular structures are characteristic hallmarks of neurodegeneration. The main research has focused to mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomal networks as well as microtubular system of the cell. The sequence of specific organelle damage during pathogenesis has not been answered yet. Exposition to rotenone is used for simulation of neurodegenerative changes in SH-SY5Y cells, which are widely used for in vitro modelling of Parkinson´s disease pathogenesis. Intracellular effects were investigated in time points from 0 to 24 h by confocal microscopy and biochemical analyses. Analysis of fluorescent images identified the sensitivity of organelles towards rotenone in this order: microtubular cytoskeleton, mitochondrial network, endoplasmic reticulum, Golgi apparatus and lysosomal network. All observed morphological changes of intracellular compartments were identified before alphaS protein accumulation. Therefore, their potential as an early diagnostic marker is of interest. Understanding of subcellular sensitivity in initial stages of neurodegeneration is crucial for designing new approaches and a management of neurodegenerative disorders.

Respiratory Function and Dysfunction in Parkinson-Type Neurodegeneration.

Parkinson's disease (PD) is most commonly manifested by the presence of motor symptoms. However, non-motor symptoms occur several years before the onset of motor symptoms themselves. Hallmarks of dysfunction of the respiratory system are still outside the main focus of interest, whether by clinicians or scientists, despite their indisputable contribution to the morbidity and mortality of patients suffering from PD. In addition, many of the respiratory symptoms are already present in the early stages of the disease and efforts to utilize these parameters in the early diagnosis of PD are now intensifying. Mechanisms that lead to the development and progression of respiratory symptoms are only partially understood. This review focuses mainly on the comparison of respiratory problems observed in clinical studies with available findings obtained from experimental animal models. It also explains pathological changes observed in non-neuronal tissues in subjects with PD.

FLIM analysis of intracellular markers associated with the development of Parkinson's disease in cellular model.

Parkinson's disease (PD) is currently the second most common neurodegenerative disorder in the world. Major features of cell pathology of the disease include the presence of cytoplasmic inclusions called Lewy bodies, which are composed of aggregated proteins. The presence of Lewy's body is associated with more advanced stages of the disease when considering irreversible changes. Precise identification of the disease stage at a cellular level presents the critical tool in developing early diagnostics and/or prevention of PD. The aim of our work is to introduce sensitive microscopic analysis in living cells, focused on initial intracellular changes and thus capable to detect earlier stages of the disease.

Effects of atosiban on stress-related neuroendocrine factors.

Atosiban, an oxytocin/vasopressin receptor antagonist, is used to decrease preterm uterine activity. The risk of preterm delivery is undoubtedly associated with stress, but potential side effects of atosiban on neuroendocrine functions and stress-related pathways are mostly unknown. These studies were designed to test the hypothesis that the chronic treatment of rats with atosiban modulates neuroendocrine functions under stress conditions. Male rats were treated (osmotic minipumps) with atosiban (600 µg/kg per day) or vehicle and were restrained for 120 min/day for 14 days. All animals were treated with a marker of cell proliferation 5-bromo-2-deoxyuridine. Anxiety-like behavior was measured using an elevated plus-maze. Treatment with atosiban failed to modify plasma concentrations of the stress hormones ACTH and corticosterone, but led to a rise in circulating copeptin. Atosiban increased prolactin levels in the non-stressed group. Oxytocin receptor mRNA levels were increased in rats exposed to stress. Treatment with atosiban, in both control and stressed animals, resulted in a decrease in oxytocin receptor gene expression in the hypothalamus. No changes were observed in vasopressin receptor 1A and 1B gene expression. The decrease in hippocampal cell proliferation induced by stress exposure was not modified by atosiban treatment. This study provides the first data, to our knowledge, revealing the effect of atosiban on gene expression of oxytocin receptors in the brain. Atosiban-induced enhancement of plasma copeptin indicates an elevation in vasopressinergic tone with potential influence on water-electrolyte balance.