Tag Archives: Parkinson’s disease

Systemic inflammation biomarkers in 6-OHDA- and LPS-induced Parkinson’s disease in rats

Zh. Oliynyk*, M. Rudyk, V. Svyatetska, T. Dovbynchuk, G. Tolstanova, L. Skivka

ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine;
*e-mail: ojankin@yahoo.com

Received: 14 December 2021; Accepted: 21 January 2022

Hematological and immunological markers of systemic inflammation were studied in 6-hydroxydopamine (6-OHDA)- and lipopolysaccharide (LPS)-induced models of Parkinson’s disease (PD). Experiments were carried out on adult male Wistar rats: 1 – intact animals; 2 – sham-operated animals and 3 – 6-OHDA- and LPS-lesioned animals. PD development was confirmed by the results of behavioral testing (apomorphine test, open field test) and immunohistochemical detection of the loss of dopaminergic neurons. Hematological indices (complete blood count and differential leukocyte count (DLC)) were examined using hematological analyser. Immunological indices included phenotypic (CD206 and CD80/86) and metabolic (oxidative metabolism and phagocytic activity) characteristics of circulating monocytes (Mo) and granulocytes (Gr), which were determined by flow cytometry, as well as plasma levels of C-reactive protein, which were determined by ELISA. LPS-induced PD was associated with neutrophilia, 1.9 times increased neutrophil-to-lymphocyte ratio, 3 times increased platelet-to-lymphocyte ratio, and 3 times increased systemic immune inflammation index as compared to intact animals. Functional profile of circulating phagocytes from LPS-lesioned animals was characterized by the pro-inflammtory metabolic shift, as was indicated by 5 times increased oxidative metabolism indices and up-regulated CD80/86 expression along with decreased phagocytic activity and CD206 expression. 6-OHDA-lesioned rats demonstrated decreased DLC indices as compared to intact and sham-operated rats. Functional profile of circulating phagocytes in this model was characterized by anti-inflammatory shift. The results obtained from this study demonstrated that stereotaxic LPS-induced PD is appropriate rodent model for the study of systemic inflammation which is inherent for the disease pathophysiology.

Diazepinone effect on liver tissue respiration and serum lipid content in rats with a rotenone model of Parkinson’s disease

L. Ya. Shtanova1,2*, P. I. Yanchuk1, S. P. Vesеlsky1,
O. V. Tsymbalyuk1, T. V. Vovkun2, V. S. Moskvina2, O. V. Shablykina2,
S. L. Bogza2, V. N. Baban1, A. A. Kravchenko3, V. P. Khilya2

1Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
2Taras Shevchenko National University of Kyiv, Ukraine;
3Chuiko Institute of Surface Chemistry, National Academy of Sciences, Kyiv;
*e-mail: shtanova@ukr.net

Received: 5 March 2020; Accepted: 13 November 2020

Parkinson’s disease (PD) is a chronic and progressive age-related neurodegenerative disorder. Accumulation of α-synuclein aggregates, oxidative stress, mitochondrial dysfunction and lipid metabolism  disturbance are thought to be the key violations at PD pathogenesis. Despite long-time  research the causes of PD occurrence are not yet clear. We investigated the influence of diazepinon, a new derivative of benzodiazepine, on liver tissue respiration (LTR), serum lipid content and  behavioral parameters of rats with modeled PD induced by intraperitoneal injections of 2.0 mg/kg rotenone (ROT) within 28 days. LTR was assessed using the polarograph LP-9. Blood samples for biochemical analysis were collected from the inferior vena cava. The behavioral parameters of rats were studied by the open field test. We showed  that in rats with ROT – induced PD the coefficient of liver oxygen consumption was decreased by 33.5% (P < 0.001), the serum content of phospholipids, cholesterol, cholesterol esters, free fatty acids and triglycerides was reduced by 21.4% (P < 0.001), 28.8% (P < 0.001), 26.8% (P < 0.001), 30.3% (P < 0.01) and 41.5% (P < 0.001) respectively and the motor disorders were detected. Diazepinone application resulted in a full recovery of  LTR,  serum concentration of phospholipids, partial recovery of serum free fatty acids and triglycerides content and significant improvement of motor behavior. However  diazepinone did not affect the reduced concentration of cholesterol and cholesterol esters in the serum of rats with simulated PD.

Oxidative stress regulation in the yeast Ogataea polymorpha producer of human α-synuclein

N. V. Hrushanyk1, O. V. Stasyk2, O. G. Stasyk1*

1Ivan Franko National University of Lviv, Ukraine;
2Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
*e-mail: olenastasyk@gmail.com

Received: 02 March 2020; Accepted: 25 June 2020

In this study we analyzed how exogenous glucose levels affect enzymatic and non-enzymatic antioxidant defense systems and markers of oxidative stress in cells of the methylotrophic yeast Ogataea polymorpha producing recombinant human α-synuclein, implicated in pathogenesis of neurodegenerative Parkinson’s disease (PD). We found that glucose depletion up-induced activity of antioxidant enzymes superoxide dismutase, and catalase, and increased content of reduced and oxidized glutathione in the cells cultivated in the medium with 0.1% glucose, as compared to physiological growth condition (1% glucose-containing medium). In addition, low glucose concentration in the medium upregulated content of proteins carbonyl groups and of products of lipid peroxidation. Notably, the shift in the equilibrium toward pro-oxidant changes was similar for recombinant α-synuclein producer and parental wild-type strain. Thus, glucose limitation leads to the overproduction of reactive oxygen species in the methylotrophic yeast cells independently of the recombinant human α-synuclein production.