LPS-induced sickness behavior is not affected by selenium but is switched off by psychogenic stress in rats

Mazuco, Túlio R. R.; Biondi, Thalles F.; Silva, Ericka P.; Bernardi, Maria Martha; Kirsten, Thiago Berti

doi:10.1007/s11259-019-09766-8

Cited by 9 publications

(9 citation statements)

References 44 publications

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“…Mounting evidence suggests the involvement of inflammasome during LPS-induced sickness behavior. LPS reduces mobility and locomotion and increases pro-inflammatory cytokines like IL-1β and IFN-gamma in rats; these are characteristics of sickness behavior ( 35 ). Other cytokines like TNF-α and IL-6 were also increased by LPS administration in rodents ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Dimethyl Fumarate Alleviates NLRP3 Inflammasome Activation in Microglia and Sickness Behavior in LPS-Challenged Mice

et al. 2021

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NLRP3 inflammasome activation contributes to several pathogenic conditions, including lipopolysaccharide (LPS)-induced sickness behavior characterized by reduced mobility and depressive behaviors. Dimethyl fumarate (DMF) is an immunomodulatory and anti-oxidative molecule commonly used for the symptomatic treatment of multiple sclerosis and psoriasis. In this study, we investigated the potential use of DMF against microglial NLRP3 inflammasome activation both in vitro and in vivo. For in vitro studies, LPS- and ATP-stimulated N9 microglial cells were used to induce NLRP3 inflammasome activation. DMF’s effects on inflammasome markers, pyroptotic cell death, ROS formation, and Nrf2/NF-κB pathways were assessed. For in vivo studies, 12–14 weeks-old male BALB/c mice were treated with LPS, DMF + LPS and ML385 + DMF + LPS. Behavioral tests including open field, forced swim test, and tail suspension test were carried out to see changes in lipopolysaccharide-induced sickness behavior. Furthermore, NLRP3 and Caspase-1 expression in isolated microglia were determined by immunostaining. Here we demonstrated that DMF ameliorated LPS and ATP-induced NLRP3 inflammasome activation by reducing IL-1β, IL-18, caspase-1, and NLRP3 levels, reactive oxygen species formation and damage, and inhibiting pyroptotic cell death in N9 murine microglia via Nrf2/NF-κB pathways. DMF also improved LPS-induced sickness behavior in male mice and decreased caspase-1/NLRP3 levels via Nrf2 activation. Additionally, we showed that DMF pretreatment decreased miR-146a and miR-155 both in vivo and in vitro. Our results proved the effectiveness of DMF on the amelioration of microglial NLRP3 inflammasome activation. We anticipate that this study will provide the foundation consideration for further studies aiming to suppress NLRP3 inflammasome activation associated with in many diseases and a better understanding of its underlying mechanisms.

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Section: Discussionmentioning

confidence: 99%

Dimethyl Fumarate Alleviates NLRP3 Inflammasome Activation in Microglia and Sickness Behavior in LPS-Challenged Mice

et al. 2021

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“…The mice were housed at Paulista University (Sao Paulo, Brazil) under standard conditions. The mice housing, nutritional conditions, and the daily handling and care were the same as previously described by our group (Mazuco et al, 2019). They were housed in polypropylene cages (34.5 × 14 × 19 cm; maximum of 5 mice per cage) with microisolator system (Tecniplast, Buguggiate, Italy), controlled temperature (23 ± 2°C), and humidity (55%–65%), with artificial lighting (12‐h light/12‐h dark cycle, lights on at 7:00 a.m.).…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, when analyzed together with other neuroimmune parameters, such as the activation of glial cells, it is used to evaluate the expression of sickness behavior in rodents (Dantzer & Kelley, 2007; Kirsten et al, 2020; Larson & Dunn, 2001). Locomotion frequency (number of floor units entered with all four paws), rearing frequency, total immobility time (s), and time (s) spent in peripheral and central zones were evaluated for each mouse (5 min per test) as previously described (Mazuco et al, 2019). The test room was small and with dim lighting, isolated from the experimenter, and with a video camera mounted above the arena to collect the data, which were analyzed after the end of the experiment.…”

Section: Methodsmentioning

confidence: 99%

Bate palmas mutant mice as a model of Kabuki syndrome: Higher susceptibility to infections and vocalization impairments?

Kirsten

Silva

Biondi

et al. 2022

J of Neuroscience Research

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The recessive mutant mouse bate palmas (bapa) arose from N-ethyl-N-nitrosourea mutagenesis. Previous studies of our group revealed some behavioral impairments and a mutation in the lysine (K)-specific methyltransferase 2D (Kmt2d) gene. Because mutations in the KMT2D gene in humans are mainly responsible for Kabuki syndrome, this study was proposed to validate bapa mice as a model of Kabuki syndrome.Besides other symptoms, Kabuki syndrome is characterized by increased susceptibility to infections and speech impairments, usually diagnosed in the early childhood. Thus, juvenile male and female bapa mice were studied in different developmental stages (prepubertal period and puberty). To induce sickness behavior and to study infection susceptibility responses, lipopolysaccharide (LPS) was used. To study oral communication, ultrasonic vocalizations were evaluated. Behavioral (open-field test) and central (astrocytic glial fibrillary acidic protein [GFAP] and tyrosine hydroxylase [TH]) evaluations were also performed. Control and bapa female mice emitted 31-kHz ultrasounds on prepubertal period when exploring a novel environment, a frequency not yet described for mice, being defined as 31-kHz exploratory vocalizations. Males, LPS, and puberty inhibited these vocalizations. Bapa mice presented increased motor/ exploratory behaviors on prepubertal period due to increased striatal TH expression, revealing striatal dopaminergic system hyperactivity. Combining open-field behavior and GFAP expression, bapa mice did not develop LPS tolerance, that is, they remained expressing signs of sickness behavior after LPS challenge, being more susceptible to infectious/inflammatory processes. It was concluded that bapa mice is a robust experimental model of Kabuki syndrome.

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“…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%

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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LPS-induced sickness behavior is not affected by selenium but is switched off by psychogenic stress in rats

Cited by 9 publications

References 44 publications

Dimethyl Fumarate Alleviates NLRP3 Inflammasome Activation in Microglia and Sickness Behavior in LPS-Challenged Mice

Dimethyl Fumarate Alleviates NLRP3 Inflammasome Activation in Microglia and Sickness Behavior in LPS-Challenged Mice

Bate palmas mutant mice as a model of Kabuki syndrome: Higher susceptibility to infections and vocalization impairments?

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

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