Effect of a water-soluble form of dihydroquercetin on age-dependent LPS-induced gliovascular remodeling of the substantia nigra in rats
- Authors: Alalykina E.S.1, Sergeyeva T.N.1, Ananyan M.А.2, Chuchkov V.M.1, Sergeyev V.G.1,3
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Affiliations:
- Udmurt State University
- Advanced Technologies Ltd.
- Izhevsk State Medical Academy
- Issue: Vol 161, No 3 (2023)
- Pages: 61-70
- Section: Original Study Articles
- Submitted: 30.01.2024
- Accepted: 26.03.2024
- Published: 27.05.2024
- URL: https://j-morphology.com/1026-3543/article/view/626214
- DOI: https://doi.org/10.17816/morph.626214
- ID: 626214
Cite item
Abstract
BACKGROUND: Neuroinflammation is a key pathophysiological mechanism in age-related neurodegenerative diseases such as Parkinson's disease. Dihydroquercetin's water-soluble form (DHQ-WF) is considered a promising agent capable of inhibiting the neuroinflammatory process. Nevertheless, uncertainties persist regarding the cellular and molecular mechanisms governing its effects, taking into account nervous tissue's gliovascular organization.
AIM: To study structural changes of microcirculatory vessels and functional responses of micro- and astroglial cells in the substantia nigra of young and old rats in response to intranigral injection of lipopolysaccharide (LPS) and subsequent oral administration of DHQ-WF.
MATERIALS AND METHODS: Young (250–320 g) and old (390–450 g) Wistar rats were injected into the substantia nigra using a stereotaxic device with 2 μL of LPS solution at a concentration of 0.01 μL/mL (experimental groups; n=24) or 2 μL of sterile saline (control groups; n=12). Half of the animals in the experimental groups (6 animals of each age group) received 2 ml of a solution containing DHQ-WF ("Taxifolin aqua"; Advanced Technologies Ltd., Russia) at a concentration of 3 mg/mL by gavage daily for 8 weeks. At the end of the experiment, the animals were transcardially perfused with 4% paraformaldehyde, the brain was extracted and frozen on dry ice. Cryostat sections obtained on the cryotome were stained with FITC-labelled tomato lectin for the detection of vascular endothelium and antibodies against GFAP and CD-11β for the immunohistochemical detection of astrocytes and microglia, respectively. The length and number of vessels and their branches were counted using AngioTool software. The areas of glial cell bodies and their processes were measured using the morphometric software ImagePro Inside 8.0.
RESULTS: 8 weeks after LPS administration into the substantia nigra (SN) of old rats, a significant excess of areas occupied by cell bodies and processes of microglial and astroglial cells, as well as the number of vessels on the standard plot, was found both in young animals that had experienced similar effects and in old control animals. Oral administration of DHQ-WF to rats significantly reduced LPS-induced glial activation in young and old animals. In addition, administration of DHQ-WF to old animals reduced the intensity of microvascular SN remodeling induced by LPS administration.
CONCLUSIONS: Administration of LPS to the SN of rats of different ages causes neuroinflammation, which is maximally expressed in aged animals. In addition, LPS-induced microvessel angiogenesis is observed in aged animals. Administration of DHQ-WF for 8 weeks significantly reduces these LPS-induced changes, which allows us to consider it as a promising anti-neuroinflammatory agent.
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About the authors
Elena S. Alalykina
Udmurt State University
Email: alena-immun@yandex.ru
ORCID iD: 0009-0006-3510-0337
SPIN-code: 5364-8013
Russian Federation, Izhevsk
Tatyana N. Sergeyeva
Udmurt State University
Email: tnbio@ya.ru
ORCID iD: 0000-0001-8273-8348
SPIN-code: 9300-2217
Russian Federation, Izhevsk
Michail А. Ananyan
Advanced Technologies Ltd.
Email: nanoindustry@mail.ru
ORCID iD: 0009-0007-9019-6981
SPIN-code: 5172-9152
Dr. Sci. (Engineering)
Russian Federation, MoscowVictor M. Chuchkov
Udmurt State University
Email: vmchuchkov@gmail.com
ORCID iD: 0000-0002-9959-689X
SPIN-code: 2347-2890
MD, Dr. Sci. (Medicine), Professor
Russian Federation, IzhevskValeriy G. Sergeyev
Udmurt State University; Izhevsk State Medical Academy
Author for correspondence.
Email: cellbio@ya.ru
ORCID iD: 0000-0002-5211-1832
SPIN-code: 1476-3236
Dr. Sci. (Biology), Assistant Professor
Russian Federation, Izhevsk; IzhevskReferences
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