Putative involvement of sirtuin modulators in LPS-induced sickness behaviour in mice
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Ranadive, Niraja
Mudgal, Jayesh
Zhang, Yuqing
Govindula, Anusha
Anoopkumar-Dukie, Shailendra
Davey, Andrew K
Grant, Gary D
Nampoothiri, Madhavan
Arora, Devinder
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Abstract
NAD+-dependent histone deacetylases (sirtuins 1-7) have been shown to be involved in various pathophysiological conditions including their involvement in cardiovascular, cancerous, neurodegenerative, immune dysregulation and inflammatory conditions. This study investigates the inflammomodulatory potential of resveratrol (RES), a sirtuin activator and sirtinol (SIR), a sirtuin inhibitor in lipopolysaccharide (LPS)-induced model of sickness behaviour in mice. Male Swiss albino mice were divided into five groups (n = 6) consisting of saline (SAL), LPS, RES, SIR, and fluoxetine (FLU) respectively, each group except LPS was prepared by intraperitoneally (i.p.) administration of SAL (10 mL/kg), RES (50 mg/kg), SIR (2 mg/kg) and FLU (10 mg/kg). Thirty minutes after the treatments, all the groups, except SAL were administered LPS (2 mg/kg, i.p.). The behavioural assays including, open field test, forced swim test, and tail suspension tests were conducted 1 h after LPS challenge. LPS administration significantly reduced the locomotor activity along with inducing a state of high immobility and that was prevented by pretreatment with RES and SIR. Further, various proinflammatory cytokines (TNF-α, IL-6, and IL-1β), and oxidative stress markers (MDA and GSH) were found to be significantly elevated in the brain homogenates after LPS treatment. SIR pretreatment abrogated the LPS-induced neuroinflammatory and oxidative stress changes, whereas RES was only effective in reducing the oxidative stress and TNF-α levels. The results of this study speculate that the role of SIRT modulators in neuroinflammatory conditions could vary with their dose, regimen and chemical properties. Further studies with detailed molecular and pharmacokinetic profiling will be needed to explore their therapeutic potentials.
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Metabolic Brain Disease
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© The Authors 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
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Subject
Metabolic medicine
Pharmacology and pharmaceutical sciences
Clinical sciences
Neurosciences
Biological psychology
Cytokines
Neuroinflammation
Resveratrol
SIRT
Sickness behaviour
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Kinra, M; Ranadive, N; Mudgal, J; Zhang, Y; Govindula, A; Anoopkumar-Dukie, S; Davey, AK; Grant, GD; Nampoothiri, M; Arora, D, Putative involvement of sirtuin modulators in LPS-induced sickness behaviour in mice, Metabolic Brain Disease, 2022