Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents

Huang, Huijie; Zhu, Xiaocang; Han, Qiu-Qin; Wang, Yalin; Yue, Na; Wang, Jing; Yu, Rui; Li, Bing; Wu, Gen-Cheng; Liu, Qiong; Yu, Jin

doi:10.1016/j.bbr.2017.02.040

Cited by 98 publications

(73 citation statements)

References 58 publications

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“…For the forced swimming test, rats or mice were individually put into 18- or 15-cm-diameter glass cylinder filled to 30 or 20 cm with 23 ± 1 °C water, respectively, as we described before [37]. During analysis of the recordings, immobility was defined as the absence of all movement except motions required maintaining the animal’s head above the water.…”

Section: Methodsmentioning

confidence: 99%

Activation of P2X7 receptor and NLRP3 inflammasome assembly in hippocampal glial cells mediates chronic stress-induced depressive-like behaviors

Yue

Huang

Zhu

et al. 2017

J Neuroinflammation

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258

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BackgroundIn recent years, proinflammatory cytokine interleukin-1β (IL-1β) was considered to play a critical role in the pathogenesis of depression. In addition, P2X7 receptor (P2X7R), a member of the purinergic receptor family, which is predominantly present on microglia, as well as on astrocytes and neurons in lesser amounts in the central nervous system, was suggested to be involved in the processing and releasing of IL-1β. Here, we investigated the role of P2X7R in the pathogenesis of depression.MethodsMale Sprague-Dawley rats were subjected to chronic unpredictable stressors (CUS) for 3 weeks. At the end of week 1, 2, and 3, extracellular ATP, caspase 1, IL-1β, and components and activation of NLRP3 inflammasome (nucleotide-binding, leucine-rich repeat, pyrin domain containing 3) were evaluated as biomarker of neuroinflammation. In separate experiments, the rats were microinjected with P2X7R agonists ATP, BzATP, and saline into the hippocampus, respectively, or exposed to CUS combined with hippocampal microinjection with P2X7R antagonist, BBG and A438079, and saline, respectively, for 3 weeks, followed by exposed to forced swimming test and open-field test. Moreover, we also evaluated the depressive and anxiety-like behavior of P2X7-null mice in forced swimming test, open-field test, and elevated plus maze.ResultsAlong with stress accumulation, extracellular ATP, cleaved-caspase 1, IL-1β, and ASC were significantly enhanced in the hippocampus, but P2X7R and NLRP3 were not. Immunoprecipitation assay indicated that along with the accumulation of stress, assembly of NLRP3 inflammasome and cleaved caspase 1 in NLRP3 inflammasome were significantly increased. Moreover, antagonists of P2X7R, either BBG or A438079, prevented the development of depressive-like behaviors induced by chronic unpredictable stress in rats. Meanwhile, we could not observe any depressive-like or anxiety-like behaviors of P2X7-null mice after they had been exposed to CUS. The results implied that P2X7 knockout could impede the development of depressive-like and anxiety-like behaviors induced by CUS. In contrast, chronic administration of agonists of P2X7R, either ATP or BzATP, could induce depressive-like behaviors.ConclusionsThe activation of P2X7R and subsequent NLRP3 inflammasome in hippocampal microglial cells could mediate depressive-like behaviors, which suggests a new therapeutic target for the prevention and treatment of depression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0865-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Activation of P2X7 receptor and NLRP3 inflammasome assembly in hippocampal glial cells mediates chronic stress-induced depressive-like behaviors

Yue

Huang

Zhu

et al. 2017

J Neuroinflammation

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258

174

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“…Our analyses also generate new hypotheses; genes associated with taking N06A (antidepressants) showed enrichment in the gene set for the synthesis and secretion and diacylation of ghrelin, a gut-derived hormone 29 . Previous studies have described an antidepressant-like role of ghrelin 30,31 . This line of evidence suggests that testing a pharmacological effect of ghrelin on depression may be worthwhile.…”

Section: Discussionmentioning

confidence: 92%

Genetic analyses of medication-use and implications for precision medicine

Byrne

Zheng

et al. 2018

Preprint

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13It is common that one medication is prescribed for several indications, and conversely that 14 several medications are prescribed for the same indication, suggesting a complex biological 15 network for disease risk and its relationship with pharmacological function. Genome-wide 16 association studies (GWASs) of medication-use may contribute to understanding of 17 disease etiology, generation of new leads relevant for drug discovery and quantify prospects 18 for precision medicine. We conducted GWAS to profile self-reported medication-use from 23 19categories in approximately 320,000 individuals from the UK Biobank. A total of 505 20 independent genetic loci that met stringent criteria for statistical significance were identified. 21We investigated the implications of these GWAS findings in relation to biological 22 mechanism, drug target identification and genetic risk stratification of disease. Amongst the 23 medication-associated genes were 16 known therapeutic-effect target genes for medications 24 from 9 categories. 25 26

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“…Researchers have suggested that anxiety disorders impair the regular functions of the hypothalamic-pituitary-adrenal (HPA) axis, causing an increase in appetite [76] due to alterations in the two hormones, ghrelin and leptin. Symptoms of anxiety have been reported to be negatively associated with levels of leptin [77,78], while ghrelin was found to have an anxiolytic effect in animal studies [79,80] following induced stress. Clearly, further research is needed to better understand the pathways that link obesity and anxiety.…”

Section: Research Question 4: What Other Factors Are Significantly Asmentioning

confidence: 99%

Nutritional Factors, Physical Health and Immigrant Status Are Associated with Anxiety Disorders among Middle-Aged and Older Adults: Findings from Baseline Data of The Canadian Longitudinal Study on Aging (CLSA)

Davison

Lin

Tong

et al. 2020

IJERPH

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The main purpose of this study was to compare the lifetime prevalence of anxiety disorders among foreign-born and Canadian-born adults in middle and later life. Using baseline data of the Canadian Longitudinal Study on Aging (2010)(2011)(2012)(2013)(2014)(2015), multivariable binary logistic regression was conducted to investigate anxiety diagnosis and immigrant status, while controlling for socio-economic, health-related, and nutrition covariates. Of 26,991 participants (49.3% men, 82.5% Canadian born, 58.5% aged 45-65 years), the overall prevalence of self-reported physician diagnosis of anxiety disorders was 8.5%, with immigrants being lower than Canadian-born respondents (6.4% vs. 9.3%, p < 0.001). After accounting for all covariates, the adjusted odds ratio (aOR) for anxiety disorders was lower among immigrants (aOR = 0.77, 95% CI: 0.67-0.88) compared to those who were Canadian born. Identified risk factors included: younger age (aORs = 1.79-3.52), being a woman (aOR = 1.25, 95% CI: 1.07-1.46), single status (aOR = 1.27, 95% CI: 1.09-1.48), lower income (aORs = 1.28-2.68), multi-morbidities (aORs = 2.73-5.13), chronic pain (aOR = 1.31, 95% CI: 1.18-1.44), lifetime smoking ≥ 100 cigarettes (aOR = 1.35, 95% CI: 1.23-1.48), BMI < 18.5 (aOR = 1.87, 95% CI: 1.20-2.92), body fat ≥ 26% (aORs = 1.28-1.79), fruit and vegetable intake (<3/day; aORs = 1.24-1.26), and pastry consumption (>1/day; aOR = 1.55, 95% CI: 1.12-1.15) (p < 0.05). Targeting socio-economic and nutritional risk factors may reduce the burden of anxiety disorders in middle and late adulthood.

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Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents

Cited by 98 publications

References 58 publications

Activation of P2X7 receptor and NLRP3 inflammasome assembly in hippocampal glial cells mediates chronic stress-induced depressive-like behaviors

Activation of P2X7 receptor and NLRP3 inflammasome assembly in hippocampal glial cells mediates chronic stress-induced depressive-like behaviors

Genetic analyses of medication-use and implications for precision medicine

Nutritional Factors, Physical Health and Immigrant Status Are Associated with Anxiety Disorders among Middle-Aged and Older Adults: Findings from Baseline Data of The Canadian Longitudinal Study on Aging (CLSA)

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