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

Yu, Xu-Ben; Dong, Rongrong; Wang, Hui; Lin, Jingran; An, Yunqi; Du, Yong; Tang, Shuming; Mei, Hu; Long, Yan; Sun, Hongbin; Kong, Ling–Yi; Hong, Hao

doi:10.1007/s00213-015-4136-2

Cited by 31 publications

(19 citation statements)

References 52 publications

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“…We previously identified CysLT 1 R signaling as a novel pro-inflammatory pathway in mice and suggested it as a potential therapeutic target for depression [18] . Here, we demonstrated that a single injection of LPS (0.5 mg/kg, ip) produced depressive-like behaviors accompanied by neuroinflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, several studies on CysLT 1 R have focused on its novel pathophysiological role in CNS disorders, such as cognitive impairment [14] , cerebral ischemia [15] , brain trauma [16] and experimental autoimmune encephalomyelitis [17] . We recently reported that CysLT 1 R knockdown in the mouse hippocampus prevented the CMS-induced depressive-like phenotype and neuroinflammation [18] . To further confirm the role of CysLT 1 R in depression, we investigated whether hippocampal CysLT 1 R knockdown or blockade repressed depressive-like behaviors and neuroinflammatory responses in LPS-treated mice.…”

Section: Acta Pharmacologica Sinicamentioning

confidence: 99%

“…The lentivirus generation was performed according to the previously described protocol [18] . All surgeries were conducted under aseptic conditions.…”

Section: Cyslt 1 R Knockdown Experimentsmentioning

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: Acta Pharmacologica Sinicamentioning

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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“…TST. The TST was carried out in mice as described previously [25]. Briefly, mice were moved from the housing room to the test room in their home cages and allowed to adapt to the new environment for at least 1 h before testing.…”

Section: Methodsmentioning

confidence: 99%

Lovastatin Prevents Depressive Behaviors and Increased Hippocampal Neurogenesis in Streptozotocin-Induced Diabetic Mice

Tang

Zhang

et al. 2019

Pharmacology

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Depression is a progressive and chronic syndrome and commonly related to several neuropsychiatric comorbidities, of which depression is the most studied. Population-based studies have suggested a positive role of statins in ameliorating depression risk. However, the role of statins in the treatment of diabetes-related depression has not been well examined. Herein, we investigated the effects of lovastatin (LOV) on depressive phenotypes in streptozotocin-induced diabetic mice. The data suggested that the treatment of LOV at 10 or 20 mg/kg for 3 weeks markedly prevented diabetesassociated depressive behaviors reflected by better performance in the sucrose preference test, tail suspension test, and novelty-suppressed feeding test. The study further showed that these treatments improved the hippocampal neurogenesis as evidenced by increased bromodeoxyuridine-positive cells in the dentate gyrus with higher expression of mature brain-derived neurotrophic factor and increased phosphorylation of cAMP-response element-binding protein. As expected, diabetic mice treated with LOV showed significant improvement of hyperlipidemia rather than hyperglycemia. These results suggest that LOV may be employed as a drug for the treatment of diabetes-related depression.

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“…Ultimately, the success of immunopsychiatry will be judged on its ability to deliver new or repurposed immunotherapies that meaningfully enhance the lives of patients suffering from mental illnesses. The finding from Yu et al that the cysteinyl leukotriene receptor 1 mediates the link between stress and inflammation and depressive behaviour is one example where new mechanistic insights could identify novel treatment targets (Yu et al 2015).…”

mentioning

confidence: 99%

Immune influences on the brain: new findings and implications for treatment

2016

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

Abstract: Hippocampal CysLT1R participates in depression, and knockdown of hippocampal CysLT1R prevents CMS-induced depressive-like behaviors and neuroinflammation, suggesting that suppression of CysLT1R could prevent the development of depression.

Cited by 31 publications

References 52 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

Lovastatin Prevents Depressive Behaviors and Increased Hippocampal Neurogenesis in Streptozotocin-Induced Diabetic Mice

Immune influences on the brain: new findings and implications for treatment

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