Prostaglandins mediate depressive-like behaviour induced by endotoxin in mice

Paiva, Viviane N. de; Lima, Samuel Nuno Pereira; Fernandes, Mateus M.; Soncini, Roseli; Andrade, C.A.F.; Giusti‐Paiva, Alexandre

doi:10.1016/j.bbr.2010.07.015

Cited by 88 publications

(61 citation statements)

References 28 publications

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“…In rodents, depressive symptoms can be induced by treatment with cytokines and cytokine-inducers, such as lipopolysaccharide (LPS), and by chronic mild stress (CMS) exposure [7,8] . Consistently, anti-inflammatory drugs [9] and antidepressants have been shown to suppress depressive behaviors and alterations in the levels of pro-inflammatory cytokines in response to LPS. These studies strongly suggest that inflammation is associated with depressive symptoms.…”

Section: Introductionmentioning

confidence: 82%

Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice

et al. 2017

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Evidence suggests that neuroinflammation is involved in depression and that the cysteinyl leukotriene receptor 1 (CysLT 1 R) plays a potential pathophysiological role in several types of CNS disorders. Our previous study has shown that knockdown of hippocampal CysLT 1 R in mice prevents the depressive-like phenotype and neuroinflammation induced by chronic mild stress (CMS). Here, we examined the effects of hippocampal CysLT 1 R knockdown and CysLT 1 R blockade on LPS-induced depressive-like behavior in mice. We found that injection of LPS (0.5 mg/kg, ip) caused marked increase in hippocampal CysLT 1 R expression, which was reversed by pretreatment with fluoxetine (20 mg·kg -1 ·d -1 for 7 d, ig). Knockdown of hippocampal CysLT 1 R or blockade of CysLT 1 R by pretreatment with pranlukast (0.5 mg/kg, ip) significantly suppressed LPS-induced depressive behaviors, as evidenced by decreases in mouse immobility time in the forced swimming test (FST) and tail suspension test (TST) and latency to feed in the novelty-suppressed feeding (NSF) test. Moreover, both CysLT 1 R knockdown and CysLT 1 R blockade markedly prevented LPS-induced neuroinflammation, as shown by the suppressed activation of microglia and NF-κB signaling as well as the hippocampal levels of TNF-α and IL-1β in mice. Our results suggest that CysLT 1 R may be involved in LPS-induced depressive-like behaviors and neuroinflammation, and that downregulation of CysLT 1 R could be a novel and potential therapeutic strategy for the treatment of depression, at least partially due to its role in neuroinflammation.

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Section: Introductionmentioning

confidence: 82%

Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice

et al. 2017

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“…25) In addition, an increase in prostaglandin synthesis through inflammation-induced COX-2 in the CNS is also implicated in sickness behavior. 13,22,26,27) We previously reported that genipin, a main constituent of Gardeniae Fructus, is one of the component herbs of KKT, ameliorated LPS-induced sickness behavior and inflammation in the hypothalamus and amygdala 2 h after LPS administration. 15) Therefore, it seemed likely that KKT would also attenuate LPS-induced inflammation in the hypothalamus and amygdala 2 h after LPS administration.…”

Section: Discussionmentioning

confidence: 97%

“…[1][2][3] Several studies have shown that activation of the immune system based on increases in release of inflammatory cytokines is associated with sickness behavior, 2,[4][5][6][7][8][9][10][11][12][13] but the etiological mechanism is not known in detail. Thus, there are no standard therapies for sickness behavior.…”

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confidence: 99%

Kamikihito Ameliorates Lipopolysaccharide-Induced Sickness Behavior <i>via</i> Attenuating Neural Activation, but Not Inflammation, in the Hypothalamic Paraventricular Nucleus and Central Nucleus of the Amygdala in Mice

Araki

Nishida

Hiraki

et al. 2016

Biological & Pharmaceutical Bulletin

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Sickness behavior is a series of behavioral and psychological changes that develop in those stricken with cancers and inflammatory diseases. The etiological mechanism of sickness behavior is not known in detail, and consequently there are no established standard therapies. Kamikihito (KKT), a Kampo (traditional Japanese herbal) medicine composed of 14 herbs, has been used clinically to treat psychiatric dysfunction. Previously, we found that KKT ameliorated sickness behavior in mice inoculated with murine colon 26 adenocarcinoma cells. In this study, we examined the effects of KKT on bacterial endotoxin lipopolysaccharide (LPS)-induced sickness behavior in mice. The administration of LPS caused the emotional aspects of sickness behavior, such as loss of object exploration, social interaction deficit, and depressive-like behavior. LPS also induced mRNA expression for cyclooxygenase (COX)-2, interleukin (IL)-1β and IL-6, and increased the number of c-Fos immunopositive cells in the hypothalamus and amygdala. KKT ameliorated the behavioral changes and reversed the increases in c-Fos immunopositive cells in the two brain regions, but did not influence the mRNA expression. These results suggest that KKT ameliorates sickness behavior via the suppression of neural activation without anti-inflammatory effects, and that KKT has the potential to treat sickness behavior.Key words Kamikihito; sickness behavior; lipopolysaccharide; hypothalamus; amygdala Sickness behavior refers to a set of adaptive behavioral and psychological changes, such as fatigue, anhedonia, depression, anxiety, apathy and loss of appetite, that occur in patients with cancer or infections.1-3) Several studies have shown that activation of the immune system based on increases in release of inflammatory cytokines is associated with sickness behavior, 2,4-13) but the etiological mechanism is not known in detail. Thus, there are no standard therapies for sickness behavior.The mechanism of induction of sickness behavior by immune system activation has been examined in bacterial endotoxin lipopolysaccharide (LPS)-treated animal models. Administration of LPS induces neuroinflammation and neural activation in rodent brain, and causes sickness behavior. 11,14) Neural activation in the paraventricular nucleus (PVN) of the hypothalamus and the central nucleus of the amygdala (CeA) and emotional aspects of behavioral changes such as depressive-like behavior, social behavior deficits and loss of interest continue for more than 24 h after LPS administration. 14,15) These studies suggest that neural activation of the PVN and CeA is involved in LPS-induced sickness behavior.Kamikihito (KKT) is a Kampo (Japanese herbal) medicine is used clinically to treat psychiatric dysfunctions such as anxiety, insomnia, amnesia and depression. Pharmacological studies have shown that KKT is effective for behavioral abnormalities and cognitive dysfunction induced by beta-amyloid, methyl-beta-carboline-3-carboxylate, scopolamine, delta-9-tetrahydrocannabinol, ovariectomy, and senescen...

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“…Intracerebroventricular injection of LPS induces the expression of COX-2 in endothelial cells, catalyzes the formation of PGs, and influences neural activity (second pathway). It seems PGs and inflammatory cytokines reinforce the LPS effects on feeding response (Konsman et al 2002;De Paiva et al 2010). For instance, Johnson (1997) reported that human IL-1 injection induces PG synthesis in neonatal pig brain.…”

Section: Discussionmentioning

confidence: 98%

The role of cyclooxygenase inhibitors in lipopolysaccharide-induced hypophagia in chicken

Zendehdel¹,

Baghbanzadeh²,

Yeganeh³

et al. 2015

CZECH J ANIM SCI

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Previous studies showed that cyclooxygenase 1 (COX) enzyme has an important role in lipopolysaccharide (LPS)-induced hypophagia in mammals but the effect of COX on LPS-induced hypophagia has not been studied in avian species. The current study was designed to investigate the effects of Indomethacin, a non-selective cyclooxygenase inhibitor, Aspirin (irreversible cyclooxygenase inhibitor), Piroxicam (a selective COX-1 inhibitor), and Celecoxib (a selective COX-2 inhibitor) on LPS-induced hypophagia in 3-h fooddeprived (FD 3 ) cockerels. One hundred and sixty ROSS 308 chickens were randomly divided into 5 experiments and 4 treatment groups (8 replicates in each group of experiments). Guide cannula was surgically implanted into the lateral ventricle of chickens. In Experiment 1, birds received LPS (5, 10, and 20 ng) intracerebroventricularly (ICV). In Experiment 2, chickens were intraperitoneally (i.p.) injected with Indomethacin (5 mg/kg) prior to LPS injection (20 ng; ICV). In Experiment 3, birds were i.p. injected with Aspirin (50 mg/kg) followed by LPS injection (20 ng; ICV). In Experiment 4, chickens were given LPS (20 ng; ICV) after Piroxicam injection (10 mg/kg; i.p.). In Experiment 5, chickens were injected with Celecoxib (10 mg/kg; i.p.) prior to LPS injection (20 ng; ICV). Cumulative feed intake was determined until 8 h post-injection. According to the results, LPS significantly decreased feed intake at 4 and 8 h post injection in birds (P ≤ 0.05). Furthermore, LPS-induced hypophagia was attenuated by pre-injection with Indomethacin, Aspirin, and Celecoxib (P ≤ 0.05). However, Piroxicam had no effect on LPS-induced hypophagia (P ≥ 0.05). These results suggest that presumably COX-2 mediates LPS-induced hypophagia in broilers.

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Prostaglandins mediate depressive-like behaviour induced by endotoxin in mice

Cited by 88 publications

References 28 publications

Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice

Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice

Kamikihito Ameliorates Lipopolysaccharide-Induced Sickness Behavior <i>via</i> Attenuating Neural Activation, but Not Inflammation, in the Hypothalamic Paraventricular Nucleus and Central Nucleus of the Amygdala in Mice

The role of cyclooxygenase inhibitors in lipopolysaccharide-induced hypophagia in chicken

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