Search Results (3)

Background/Objectives: As the regulatory center for basal ganglia, the substantia nigra is involved in the pathophysiology of dopaminergic dysregulation in Parkinson’s disease (PD). Increasing neuronal excitability of dopaminergic neurons by different therapeutic methods could reverse the locomotor disturbances of PD. The purpose of this study was the comparative assessment of effects induced by excitatory output from the motor cortex to the substantia nigra (SN) and to investigate the pattern of neuronal responses in an experimental rat model of rotenone-induced (intracerebral infusion) neurodegeneration and treated with bacterial melanin (BM). Methods: Thirty-three rats were divided into three groups: control or intact animals (n = 12), animals with the rotenone-induced model of PD (n = 10), and animals with the PD model and treated with BM in 48 h following the infusion (n = 11). Registration of neuronal activity from SN neurons was conducted at four weeks following the rotenone administration. High-frequency stimulation of brain cortical area M1 was performed and the background and evoked activity patterns of 622 neurons were recorded. The difference between the groups was analyzed using one-way ANOVA followed by Tukey’s test. Results: A statistically significant difference was observed between the similar proportions of post-stimulus effects registered in different groups, showing the predominance of excitatory responses in the neurons of the melanin-treated group. A comparison of the firing pattern between the SNc and SNr neurons did not reveal significant differences. Conclusions: BM treatment has the potential to enhance motor recovery after neurodegeneration in the SN. Deep brain stimulation via the cortico-nigral pathway, with the application of BM, enhances electrical activity in dopaminergic neurons of the substantia nigra and could be a potential therapeutic model for PD. Full article

The ultra-high-performance liquid chromatography high-resolution mass spectrometry (LC-ESI-HR-MS/MS) technique was used to characterize the polyphenolic fraction of the hot water infusion (WI) of inflorescences of Cannabis sativa L. Kompolti variety, commercially used for food preparations or cosmetic purposes. On water infusion extract, we applied a multidisciplinary approach, where NMR, MS, in vitro cell-free and cell-based assays coupled with in silico studies, were used to rationalize at the molecular level the effects of the major component Cannabidiol (CBD), in a model of Parkinson’s disease (PD). The phytochemical analysis by LC-MS/MS led to the tentative identification of many components belonging to different classes of polyphenols, such as phenolic acids, flavonoids, and their glycosides. CBD and cannabidiolic acid (CBDA) were also detected in good amounts in the infusion, together with several minor cannabinoids. In addition, the water infusion WI was evaluated for mineral content, total phenolic content, flavonoid content, and antioxidant capacity by DPPH and FRAP methods. Notably, our results in a cellular model of PD highlight that CBD protects against rotenone-induced cell death without recovering neuronal morphology. These biological outcomes were rationalized by an in silico approach, where we hypothesize that CBD could influence the cellular response to oxidative stress via its interaction with the Keap1/Nrf2 pathway. In summary, these results enriched the nutraceutical profile of the water infusion of the inflorescences of the Kompolti cultivar, which demonstrated a high CBD content. This study could lead to the development of dietary supplements that could help in the management of clinical symptoms related to the antioxidant activity of CBD in the pathophysiology of PD, which remains poorly characterized. Full article

Parkinson’s disease (PD) is a progressive neurological disorder marked by nigrostriatal dopaminergic degeneration. Evidence suggests that mitochondrial dysfunction may be linked to PD through a variety of different pathways, including free-radical generation and dysfunction of the mitochondrial Complex I activity. In Lewis rats, chronic systemic administration of a specific mitochondrial Complex I inhibitor, rotenone (3 mg/kg/day) produced parkinsonism-like symptoms. Increased oxidized proteins and peroxynitrite, and mitochondrial or cytosol translocation of Bim, Bax or cytochrome c in the striatum was observed after 2–4 weeks of rotenone infusion. After 28 days of systemic rotenone exposure, imunohistochemical staining for tyrosine hydroxylase indicated nigrostriatal dopaminergic neuronal cell degeneration. Characteristic histochemical (TUNEL or activated caspase-3 staining) or ultrastructural (electron microscopy) features of apoptotic cell death were present in the striatal neuronal cell after chronic rotenone intoxication. We conclude that chronic rotenone intoxication may enhance oxidative and nitrosative stress that induces mitochondrial dysfunction and ultrastructural damage, resulting in translocation of Bim and Bax from cytosol to mitochondria that contributes to apoptotic cell death in the striatum via cytochrome c/caspase-3 signaling cascade. Full article