Changes in the energy activity of blood lymphocytes and morphometric parameters of the brain in a model of brain damage in rats

1FSBI Institute of Theoretical and Experimental Biophysics, RAS, Pushchino, Russia

2Institute of Cell Biophysics, Russian Academy of Sciences

3Pushchino branch of the federal state budgetary educational institution of higher education “Russian Biotechnological University (ROSBIOTECH)”, Pushchino, Russia

Introduction . It is known that Parkinson’s disease (PD) being a neurodegenerative disease is accompanied by increased levels of reactive oxygen species, oxidative stress and impaired mitochondrial activity.

20 | Cardiometry | Issue 29. November 2023

It has been shown that the development of malignant tumors can be accompanied by disorders that mimic PD. In this regard, shifts in cellular metabolism associated with the development of true PD are of interest.

The aim of our research work was to determine the activity of the mitochondrial and glycolitic marker enzymes succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) in blood lymphocytes and the level of oxidative stress in the body in rats in an experimental model of Parkinson’s syndrome induced by the introduction of the neurotoxin 6-hydroxydopamine (6-OHDA). In addition, our aim was to investigate the effect made by the mitoKATP binding channel activator Uridine on animals with PD.

Materials and methods . The study was carried out in male Wistar rats (n=27), weighing 200-250 g, kept by the facility at the Institute of Theoretical and Experimental Biophysics at the Russian Academy of Sciences. Pathology modeling was carried out by bilateral stereotaxic injection of neurotoxin (6-OHDA) into the substantia nigra. To activate the mitochondrial ATP-dependent potassium channel (mito-KATP), an intraperitoneal administration of Uridine at a dose of 30 mg/kg body weight was used for 22 days. Determination of the activity of SDH and LDH was performed by the developed Cytobio-chemical (CBC) method under the reduction of Nitroblue tetrazolium in immobilized blood lymphocytes. Lipid peroxidation products were assessed by the amount of malondialdehyde (MDA). Histological cryotomic sections of the striatum were stained with hematoxylin and eosin.

Results . When the neurotoxin 6-OHDA was injected into the substantia nigra, the animals experienced a 70% impairment of the motor function in the rotarod test. When determining the content of lipid peroxidation products in mitochondria of the cerebral cortex and in the blood serum in the animal group with the neurotoxin, the level of MDA in mitochondria of the rat brain was 18% higher, and in the blood serum it was increased by 37% as against the reference group. The administration of

Uridine to sick animals reduced that indicator to the reference level. The introduction of the mito-KATP inhibitor - 5-HD removed the positive effect of Uridine in blood serum and led to an increase in the content of the MDA products by 45%. The CBC measurement of the SDH activity in lymphocytes in the PD rats did not show significant differences, however, the administration of Uridine to sick animals led to an increase in the SDH activity by 80% as compared to the reference group. The measurement of the LDH activity in the rats with PD reliably showed an increase in that activity type by 35% of the reference group value, and treatment with Uridine reduced that activation to the level of the reference values. The introduction of 5-HD removed the effect of Uridine both in mitochondria and cytosol of lymphocytes.

Conclusions . Thus, in a model system of Parkinson’s syndrome in rats, induced by the administration of 6-OHDA, considering blood lymphocytes, the predominance of glycolysis over oxidative phosphorylation of mitochondria was revealed. The administration of Uridine led to an increase in mitochondrial respiration by 80% and a decrease in glycolysis. An increase in lipid peroxidation was found in the blood serum of sick animals compared to the reference values that was also removed by Uridine. In sick animals, an increase in the number of dead neurons in the striatum and their restoration in rats with Uridine was also detected. An inhibitory analysis showed that the therapeutic effect of Uridine is associated with the activation of the mi-toK-ATP channel.