Leukotriene D4 induces amyloid-β generation via CysLT1R-mediated NF-κB pathways in primary neurons

Wang, Xiao Yun; Tang, Su Su; Mei, Hu; Long, Yan; Li, Yong Qi; Liao, Ming Xing; Ji, Hui; Hong, Hao

doi:10.1016/j.neuint.2013.01.002

Cited by 41 publications

(24 citation statements)

References 42 publications

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“…The pathophysiological role of CysLT 1 R, a high-affinity G protein-coupled receptor, is well documented in several inflammatory conditions. CysLT 1 R-mediated signaling is related to the NF-κB pathway in some peripheral cells [25,43,44] . Recently, the CysLT 1 R-mediated NF-κB pathway was also observed in neurons [22] .…”

Section: Discussionmentioning

confidence: 99%

“…Pre-treatment with LV-CysLT 1 R-shRNA-EGFP significantly prevented the increase in Iba1-positive cells (P=0.009; Figure 6A, 6B). In addition, treatment with pranlukast (0.3 or 0.6 mg/kg) also notably decreased the number of Iba1-positive cells (F (4,25) =7.174; LPS+Veh vs LPS+Pran (0.3 mg/kg): P=0.011; LPS+Veh vs LPS+Pran (0.6 mg/kg): P=0.004; Figure 6C, 6D).…”

Section: Hippocampal Cyslt 1 R Knockdown or Blockade Prevented Lpsindmentioning

confidence: 91%

“…Immunohistochemical detection of brain sections revealed a marked increase in the number of Iba1-positive cells in the mouse hippocampus after LPS challenge (F (4,25) =8.988; P=0.004; Figure 6A, 6B), indicating a massive activation of microglia. Pre-treatment with LV-CysLT 1 R-shRNA-EGFP significantly prevented the increase in Iba1-positive cells (P=0.009; Figure 6A, 6B).…”

Section: Hippocampal Cyslt 1 R Knockdown or Blockade Prevented Lpsindmentioning

confidence: 99%

“…Hippocampal CysLT 1 R knockdown or blockade inhibited LPSinduced activation of the NF-κB pathway and production of proinflammatory cytokines CysLT 1 R has been reported to be implicated in neuroinflammation by regulating the NF-κB signaling pathway [23][24][25][26] , and LPS exposure activates NF-κB signaling by inducing the nuclear translocation of p65 [27] . To explore whether CysLT 1 R is involved in LPS-activated NF-κB signaling, the hippocampal level of NF-κB p65 in the nuclear fraction was detected by Western blot analysis.…”

Section: Hippocampal Cyslt 1 R Knockdown or Blockade Ameliorated Lpsimentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Hippocampal Cyslt 1 R Knockdown or Blockade Prevented Lpsindmentioning

confidence: 91%

Section: Hippocampal Cyslt 1 R Knockdown or Blockade Prevented Lpsindmentioning

confidence: 99%

Section: Hippocampal Cyslt 1 R Knockdown or Blockade Ameliorated Lpsimentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2017

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“…CysLT 1 antagonists are commonly used to treat asthma and allergic rhinitis (31,32). Previous studies have reported a role for CysLTs in inflammation, vascular permeability, immune responses, tissue repair, and regeneration (28,(33)(34)(35)(36). CysLT 2 and CysLT 1 are expressed in the murine retina, and exogenous cysLTs are sufficient to induce retinal edema (37).…”

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confidence: 99%

Phenotype-based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis

Reynolds

Álvarez

Sasore

et al. 2016

Journal of Biological Chemistry

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Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization. Phenotype-based chemical screens were performed using the ChemBridge Diverset

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Knockdown of hippocampal cysteinyl leukotriene receptor 1 prevents depressive behavior and neuroinflammation induced by chronic mild stress in mice

Dong

Wang

et al. 2015

Psychopharmacology

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Leukotriene D4 induces amyloid-β generation via CysLT1R-mediated NF-κB pathways in primary neurons

Cited by 41 publications

References 42 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

Phenotype-based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis

Knockdown of hippocampal cysteinyl leukotriene receptor 1 prevents depressive behavior and neuroinflammation induced by chronic mild stress in mice

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