The mitochondrial network (MN) is a dynamic structure undergoing constant remodeling in the cell. It is assumed that perturbations to the MN may be associated with various pathologies, including Parkinson’s disease (PD). Using automatic image analysis and super-resolution microscopy, we have assessed the MN parameters in fibroblasts from patients with established hereditary PD mutations (associated with PINK1, LRRK2, and α-synuclein, as well as PINK1 and Parkin proteins simultaneously) under normal conditions and after hydrogen peroxide-induced stress. Fibroblasts with the Pink1/Parkin mutation are most different in morphology to fibroblasts obtained from conditionally healthy donors: the MN is larger, and it contains longer mitochondria and accumulated individual mitochondria. In addition to MN, we evaluated other cellular parameters, such as cytosolic and mitochondrial ROS production and mitochondrial membrane potential. It has been shown that mitochondria of fibroblasts with mutations in genes encoding PINK1, α-synuclein, and Pink/Parkin tend towards hyperpolarization and cytosolic ROS overproduction, while mitochondrial ROS production was higher only in fibroblasts with PINK1 and α-synuclein mutations.

Parkinson’s disease (PD) is a ubiquitous neurodegenerative disorder for which no effective treatment strategies are available. Existing pharmacotherapy is aimed only at correcting symptoms and slowing the progression of the disease, mainly by replenishing dopamine deficiency. It is assumed that mitochondrial dysfunction plays a key role in the pathogenesis of PD. It has been suggested that activation of specific degradation of damaged mitochondria (mitophagy) may prevent cell death. An almost exclusive way to initiate mitophagy is acidification of intracellular pH. We attempted to implement transient brain acidification using two experimental therapy strategies: forced moderate physical activity and high CO₂ inhalation. The beneficial effects of CO₂ supplementation on behavioral aspects were demonstrated in a rotenone-induced PD model. Mice treated with CO₂ restored their exploratory behavior and total locomotor activity lost after rotenone administration. Additionally, this treatment enabled the removal of impaired coordination. We have illustrated this therapeutic strategy using histological studies of brain sections to confirm the survival of nigrostriatal areas. These findings suggest that high CO₂ inhalation presumably initiates mitophagy via transient brain acidification, and can treat PD-like symptoms in a rodent rotenone model of PD.

Gi-coupled receptors, particularly cannabinoid receptors (CBRs), are considered perspective targets for treating brain pathologies, including epilepsy. However, the precise mechanism of the anticonvulsant effect of the CBR agonists remains unknown. We have found that WIN 55,212-2 (a CBR agonist) suppresses the synchronous oscillations of the intracellular concentration of Ca²⁺ ions (epileptiform activity) induced in the neurons of rat hippocampal neuron-glial cultures by bicuculline or NH₄Cl. As we have demonstrated, the WIN 55,212-2 effect is mediated by CB₁R receptors. The agonist suppresses Ca²⁺ inflow mediated by the voltage-gated calcium channels but does not alter the inflow mediated by NMDA, AMPA, and kainate receptors. We have also found that phospholipase C (PLC), protein kinase C (PKC), and G-protein-coupled inwardly rectifying K⁺ channels (GIRK channels) are involved in the molecular mechanism underlying the inhibitory action of CB₁R activation against epileptiform activity. Thus, our results demonstrate that the antiepileptic action of CB₁R agonists is mediated by different intracellular signaling cascades, including non-canonical PLC/PKC-associated pathways.

Background/Objectives: Polysaccharides are complex molecules with a wide range of biological activities that can be used in various biomedical applications. In this work, the antiulcer effect and influence on the level of pro- and anti-inflammatory cytokines of Solanum tuberosum L. polysaccharide (STP) were studied. Methods: The antiulcer effect of STP was studied in the Okabe chronic peptic ulcer model by evaluating the influence of STP on the ulcer index in Wistar rats, comparing it to omeprazole and ranitidine. Dose-effect analysis was also carried out. The level of pro- and anti-inflammatory cytokines was studied using ELISA kits. Results: After treatment in the polysaccharide groups, ulcer healing is observed in 60–80% of cases, in the omeprazole group in 50%, and in the ranitidine group in 25%. STP intravenous injections lead to the formation of a more differentiated mucous membrane; no coarse scar tissue is formed, which is typical for control and comparison drugs. Glycan causes a significant acceleration of the healing of experimental peptic ulcers in rats. STP appears to modulate pro- and anti-inflammatory cytokines. On the fourth and tenth days, a significant decrease in the levels of pro-inflammatory cytokines IL-1b and IFN-γ was noted in the polysaccharide group compared to the control group, while the level of anti-inflammatory cytokine IL-4 significantly increased. Conclusions: Intravenous administration of STP leads to the restoration of functionality and effective tissue regeneration. The antiulcer activity of STP is based on the regulation of the pro- and anti-inflammatory balance.