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Oscillation processes in synuclein-KO mouse skin microcirculation: a pilot study.

Kozlov I.O.1, Serov D.A.2, Seryogina E.S.3 Astashev M.E.2 Tankanag A.V.2 Chaprov K.D.4 Lysikova E.A.4 Zherebtsov E.A.3,5 Abramov A.Y.3,6 Dunaev A.V.1,3,
1 R&D Center of Biomedical Photonics, Orel State University, Orel, Russia
2 Institute of Cell Biophysics, Russian Academy of Science, Pushchino, Moscow region, Russia
3 Cell Physiology and Pathology Laboratory, Orel State University, Orel, Russia
4 Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
5 Optoelectronics and Measurement Techniques Laboratory, University of Oulu, Oulu, Finland
6 Department of Clinical and Movement Neurosciences, UCL Queen Square Institute
of Neurology, London, UK

Abstract

A specific role in the development of neurodegeneration during Parkinson's, Alzheimer's diseases and parkinsonism is assigned to proteins of the synuclein family which is found in the cells of the central nervous system, blood cells and endothelial cells. However, their physiological role in the body and their influence on ontogenesis is not fully understood. It is well-known the mutations in the gene encoding alpha-synuclein production and leading to neurodegeneration. The role of beta and gamma synucleins has not been fully explained and disclosed. This study focuses on the effect of synuclein knockouts on the skin microcirculation oscillations. Registration of skin perfusion parameters was performed using the laser Doppler flowmetry technique.
The mice with the following types of synuclein KO were chosen as the study subjects: by αγ-synuclein, β-synuclein, and αβγ–synuclein. Measurements were performed with preliminary sedation with combined anesthesia Zoletil injection during N2O:O2 (77:23) inhalation. The temperature was stabilized in the experimental chamber at 25 °C. For all experiments, ECG and body temperature of the animal were monitored. Skin perfusions of the hind limbs of mice were recorded using two devices: the first device was LAKK-01 (LAZMA, Russia) with emission peak 630 nm and the second one was self-developed LDF device (1064 nm) with custom signal processing.
The experiment was performed for 40 min in two stages: the baseline stage (15 min) and during local heating at 40 °C (25 min). Statistical, wavelet, spectral and bispectral analysis were used to signal processing.
Knockout mice by α-synuclein (αβγ-KO and αγ-KO groups) tended to decrease the amplitudes of skin microcirculation oscillations in the NO-independent range at baseline stage compared to the wild type. The β-synuclein knockout had no effect on baseline stage microcirculation parameters. In response to local heating, αβγ-KO and αγ-KO mice showed no changes in microcirculatory parameters, whereas the wild type demonstrated a tendency to increase the amplitudes of myogenic oscillations.
The reported study was funded by RFBR, project number 19-32-90253.
Transgenic animals were provided and supported by Bioresource Collection of IPAC RAS and Centre for Collective Use IPAC RAS facilities and equipment was used to maintain animals in the framework of the State Assignment of IPAC RAS (No. 0090-2019-0005).


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Kozlov Igor O.
Orel State University named afret I.S. Turgenev
Russia

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