Simvastatin attenuated sickness behavior and fever in a murine model of endotoxemia

Oliveira, Merelym Ketterym de; Santos, Rafaela Silva; Cabral, Layla D.M.; Vilela, Fabiana C.; Giusti‐Paiva, Alexandre

doi:10.1016/j.lfs.2020.117701

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…In our study, LPS induced a decrease in exploratory behavior in rats in OFT, depressive-like symptoms in FST, social interaction, and anorexia, allowing us to verify the ability of this endotoxin to produce characteristic sickness behavior. Sickness behavior accompanied by fever constitute a highly regulated and adaptive strategy to ght infections (Quan and Banks, 2007;Harden et al, 2015;Oliveira et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…LPS is recognized by CD14-MD2 receptors present in monocyte membranes, and it sends intracellular signals via toll-like receptor 4 (TLR-4), culminating in the activation of NF-kB and release of proin ammatory mediators (Engblom et al, 2002;Bellezza et al, 2018;Blomqvist and Engblom, 2018). The production of TNF-α and IL1-β induces the synthesis of cyclooxygenase enzyme-2 (COX-2) in the hypothalamic vascular network, resulting in an increase in the cerebral levels of prostaglandin E2 via COX-2 (Engblom et al, 2002;Kawahara et al, 2015;Blomqvist and Engblom, 2018), sickness behavior (Dantzer, 2004;de Paiva et al, 2010;Oliveira et al, 2020), and onset of LPS-induced fever (Evans et al, 2015;Garami et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, sickness behavior was evaluated by open eld test (OFT), forced swim test (FST), social interaction test, or food intake assessment 2 hours after the administration of LPS. This time point was chosen based on previous behavioral, endocrinal, and neurochemical studies (Orlandi et al, 2015;Munshi et al, 2019;Oliveira et al, 2020). LPS was dissolved in a sterile saline solution (0.9% NaCl), and curcumin was suspended in 1% carboxymethylcellulose.…”

Section: Behavioral Experimental Protocolmentioning

confidence: 99%

“…Communication between the immune system and the brain is important for the host organism to engage in (Sylvia et al, 2018) temporary and speci c defense behaviors (Mazuco et al, 2019), such as reduced locomotor and exploratory activities, social withdrawal, anorexia, and anhedonia, which together are known as sickness behavior (Dantzer, 2004;Poon et al, 2015;Nilsson et al, 2017;Oliveira et al, 2020). In addition, in ammation is often accompanied by thermal manifestations, such as fever (Poon et al, 2015;Blomqvist and Engblom, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Curcumin prevents sickness behavior and fever by the modulation of Nrf2 activity in a model of endotoxemia

Reis¹,

Oliveira²,

Rojas³

et al. 2021

Preprint

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Lipopolysaccharide (LPS) is a potent inducer of inflammation, triggering behavioral changes and fever. The present study aimed to evaluate whether pretreatment with curcumin prevents the behavioral changes and fever induced by LPS through the modulation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Male Wistar rats were pretreated for 2 consecutive days with vehicle or curcumin at doses of 25, 50, or 100 mg/kg by oral gavage. The animals intraperitoneally received either vehicle or LPS at a dose of 500 µg/kg. After 2 h, the behavioral responses were assessed through open field test (OFT), social interaction test, forced swim test (FST), and food intake assessment. The febrile response was assessed by telemetry after vehicle or LPS injection to evaluate the effect of curcumin on the thermoregulatory response during the immunological challenge. The pretreatment with curcumin at doses of 50 and 100 mg/kg prevented the reduction of distance traveled on OFT, increased the immobility time of FST, impaired social withdrawal, decreased food intake, and induced fever. In addition, at these doses, it was possible to observe a significant decrease in the plasma levels of TNF-α and IL1-β and an increase in Nrf2 translocation to the cell nucleus during the immunological challenge. Our data provide further evidence of curcumin's ability to prevent LPS-induced sickness behavior and fever possibly by a mechanism related to the modulation of Nrf2 translocation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Behavioral Experimental Protocolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Curcumin prevents sickness behavior and fever by the modulation of Nrf2 activity in a model of endotoxemia

Reis¹,

Oliveira²,

Rojas³

et al. 2021

Preprint

Self Cite

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“…The model was adapted from our previous work, which demonstrated that a single intraperitoneal injection of LPS (2 mg/kg) induces a long-term inflammatory response in aged rat hippocampus and impaired behavior performances ( Fu et al, 2014 ; Kan et al, 2016 ). Systemic levels of inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNFα), were measured by enzyme-linked immunosorbent assay (ELISA) as their levels are highly correlated with sickness behavior after LPS exposure ( Oliveira et al, 2020 ). We hypothesized that the topology structure and FC in the aged rat DMN will both change after inflammatory exposure, which may provide new insights into drug target design and new diagnostic biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Altered functional connectivity and topology structures in default mode network induced by inflammatory exposure in aged rat: A resting-state functional magnetic resonance imaging study

Liu

Feng²,

Fu³

et al. 2022

Front. Aging Neurosci.

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Inflammatory stress in anesthesia management and surgical process has been reported to induce long-term cognitive dysfunction in vulnerable aged brain, while few studies focused on the network mechanism. The default mode network (DMN) plays a significant role in spontaneous cognitive function. Changes in topology structure and functional connectivity (FC) of DMN in vulnerable aged brain following inflammatory stress-induced long-term cognitive dysfunction are rarely studied. Eighty-eight aged male rats received intraperitoneal injection of lipopolysaccharide (LPS) as treatment or equal amount of normal saline (NS) as control. Morris Water Maze (MWM) was performed to assess short- (<7 days) and long-term (>30 days) learning and spatial working memory. Enzyme-linked immunosorbent assay (ELISA) was used to measure systemic and hippocampus inflammatory cytokines. Real-time polymerase chain reaction (RT-PCR) was used to measure the changes in gene level. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to exam brain function prior to MWM on days 3, 7, and 31 after LPS exposure. Graph theory analysis was used to analyze FC and topology structures in aged rat DMN. Aged rats treated with LPS showed short- and long-term impairment in learning and spatial working memory in MWM test. Graph theory analysis showed temporary DMN intrinsic connectivity increased on day 3 followed with subsequent DMN intrinsic connectivity significantly altered on day 7 and day 31 in LPS-exposed rats as compared with controls. Short- and long-term alterations were observed in FC, while alterations in topology structures were only observed on day 3. Rats with inflammatory stress exposure may cause short- and long-term alterations in intrinsic connectivity in aged rat’s DMN while the changes in topology structures only lasted for 3 days. Inflammatory stress has prolonged effects on FC, but not topology structures in venerable aged brain.

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Hyperactivation of the amygdala correlates with impaired social play behavior of prepubertal male rats in a maternal immune activation model

Vitor-Vieira

Giusti‐Paiva

2021

Behavioural Brain Research

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Simvastatin attenuated sickness behavior and fever in a murine model of endotoxemia

Cited by 5 publications

References 38 publications

Curcumin prevents sickness behavior and fever by the modulation of Nrf2 activity in a model of endotoxemia

Curcumin prevents sickness behavior and fever by the modulation of Nrf2 activity in a model of endotoxemia

Altered functional connectivity and topology structures in default mode network induced by inflammatory exposure in aged rat: A resting-state functional magnetic resonance imaging study

Hyperactivation of the amygdala correlates with impaired social play behavior of prepubertal male rats in a maternal immune activation model

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