SYSTEMIC INFLAMMATION AS AN INDUCTOR OF DOPAMINERGIC NEURON DEGENERATION

Abstract

Some mechanisms of neuronal degeneration during endotoxemia have already been well described, but require further detail. Endotoxin is capable of activating microglial cells in the brain, which damage neurons through the synthesis and expression of proinflammatory cytokines. The endotoxin neurodegeneration hypothesis has not yet been proven, but if it is correct, then neuronal death could be reduced by reducing endotoxin-induced neuroinflammation. Therefore, drugs that reduce inflammation caused by endotoxin can be used to prevent or reduce the severity of neurodegenerative processes.

The purpose of this work was to determine a regional and temporal analysis of the response of CNS cells to a systemic inflammatory process set by intraperitoneal administration of LPS, including during the administration of dexamethasone.

Materials and methods. Wistar rats (Rappolovo) weighing 250-260 g. Commercial lipopolysaccharide (LPS) synthesized by SIGMA from E. coli O55:B5, 25 mg lyophilisate. The drug dexamethasone injection solution 4 mg/1 ml. Ampoule 1 ml No. 25 from the manufacturer KRKA. Saline solution - 9% sodium chloride solution. Isolation of total mRNA, reverse transcription RT-PCR, HPLC.

In this study, we tested the effect of a single intraperitoneal injection of a subseptic dose of LPS (1 mg/kg animal weight) in combination with the glucocorticoid dexamethasone (2 mg/kg animal) on markers of inflammation and dopamine levels in the striatum of rats at long periods after the start of the experiment.

Results. We showed that striatal cells observed an increase in the expression of TNF-α mRNA and the microglial activation marker IBA-1. However, the administration of dexamethasone did not prevent the development of endotoxin-induced neurodegeneration in the long term after the start of the experiment.
Conclusions.

1 - intraperitoneal administration of dexamethasone at a dose of 2 mg/kg of an animal 2 hours before the administration of LPS at a dose of 1 mg/kg of an animal does not prevent the development of inflammation in the central nervous system.

2 - 180 days after intraperitoneal administration of LPS at a dose of 1 mg/kg of animal weight, the content of dopamine in the striatum decreases.

About the authors

Viktoriya Maystrenko

Author for correspondence.
Email: Sch_Viktoriya@mail.ru
ORCID iD: 0000-0001-7004-7873
Russian Federation

Elena Lebedeva

Email: Lena988902@yandex.ru
ORCID iD: 0009-0003-9034-2353
Russian Federation

Ekaterina Kukushkina

Email: Eskukushkina@mail.ru
ORCID iD: 0009-0008-2441-8889
Russian Federation

Valenyina Kudrinskaya

Email: v.kudrinskaja2011@yandex.ru
ORCID iD: 0000-0002-2763-5191
Russian Federation

Tatiana Tiutiunnik

Email: t.tanjon11@yandex.ru
ORCID iD: 0000-0002-2427-9355
Russian Federation

References

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) Eco-Vector



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.