Glibenclamide alters serotonin and dopamine levels in the rat striatum and hippocampus, reducing cognitive impairment.

RATIONALE: Glibenclamide (GD) is a widely used medical drug; therefore, identifying the mechanisms underlying its pleiotropic effects in the central nervous system is urgent. OBJECTIVES: The aim of this work was to determine the ability of GD to modulate serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) transmission and to assess the dose-dependent effect of GD on cognitive function in rats during natural ageing. METHODS: In Experiment 1, rats received 10, 25, or 50 µg/kg GD intraperitoneally for 10 days. In Experiment 2, rats received 50 µg/kg GD intraperitoneally for 30 days. Spatial and working memory was assessed in the MWM and Y-maze tests, respectively. In both experiments, the levels of DA and 5-HT, their metabolites, and turnover rate were analysed by HPLC-ED in the rat hippocampus and striatum. RESULTS: Changes in DA and 5-HT levels occurred only with a dose of 50 µg/kg GD. Therefore, in the second experiment, we administered a dose of 50 µg/kg GD. At this dose, GD prevented the development of impairments in spatial and working memory. The hippocampal concentrations of DA and DOPAC decreased, and the striatal concentrations of DA, DOPAC, 5-HT, and 5-HIAA increased. CONCLUSION: One of the possible mechanisms of the precognitive effect of GD is its ability to modulate monoamine transmission. Thus, in translating our results to humans, GD can be recommended as a prophylactic agent for natural ageing to reduce the risk of developing cognitive impairments.

The relationship between serum interleukin-1ß, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α levels and clinical features in essential tremor.

BACKGROUND: In recent years, there has been discussion that essential tremor (ET) might be a neurodegenerative disease. Indicators of inflammation are considered as possible biomarkers of neurodegeneration. In this connection, the aim of our study was to identify the relationship between serum inflammation markers and clinical features in ET, including the severity of tremor, cognitive decline, depression. METHODS: The serum interleukin-1ß (IL-1ß), IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) levels were measured in 90 ET patients and 90 healthy control people of the corresponding age and gender. Fahn-Tolosa-Marin scale was used for the severity of the tremor. Cognitive function was assessed using the MoCA. Affective symptoms were measured by the Beck Depression Inventory. RESULTS: ET patients had significantly lower serum TNF-α (p < 0.01) but higher serum IL-8 (p < 0.02) and IL-10 (p < 0.01) levels compared to the control patients. The severity of tremor positively correlated with the serum IL-8 level, R = 0.3 (p < 0.01). The serum IL-6 level was higher in ET patients with cognitive impairment compared with normal cognitive ability (p < 0.01). ROC analysis showed that an IL-8 level of 4 pg/ml and higher related with a high risk of severe tremor in ET (AUC-ROC = 0.761). CONCLUSIONS: Our findings demonstrate that neuroinflammation makes a certain contribution to the development of ET.

Calpain activity in plasma of patients with essential tremor and Parkinson's disease: a pilot study.

Background: Essential tremor (ET) and Parkinson's disease (PD) are the two most common movement disorders in adults with similar clinical symptoms, which is hinting towards existence of coincident pathogenesis steps.Objectives: The objective of this report is to characterize the relationship between ET and PD severity and the activity of calcium-dependent proteases calpain in plasma.Methods: The study enrolled 12 volunteers for each condition: ET, PD, healthy. We evaluated the stage of PD on the H&Y scale in patients with PD, and the severity of tremor in patients with ET on the FTMS scale. IL-1ß, TNFα, IL6, IL10 were determined in plasma using ELISA. Calpain activity was measured using fluorescent substrate and zymography methods.Results: We demonstrated that the activity of calpains in plasma of patients with PD and ET increased 5.1 and 4.3 times, respectively. The increase of calpain activity in plasma of PD patients correlated with the content of IL-1ß, for ET such a connection was not found. At the advanced stages of PD calpain activity in plasma was significantly higher than that of the PD group at the early stage, and this increase was mediated by the increase in m-calpain activity. The increase in the tremor severity in ET did not lead to an increase in the activity of calpains in plasma.Conclusions: We observed general increase in the activity of calpains in plasma of both PD and ET patients that hints towards presence of the common steps in the pathogenesis of these diseases.