Suppression of NLRP3 inflammasome attenuates stress-induced depression-like behavior in NLGN3-deficient mice

Li, Zequn; Yan, Zhiyuan; Lan, Fujun; Dong, Yiqun; Xiong, Ye

doi:10.1016/j.bbrc.2018.05.085

Cited by 42 publications

(17 citation statements)

References 33 publications

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“…Although we did not measure the effect of astrocytic NLRP3 on integral or neuronal BDNF, the suppression of NLRP3 significantly decreased CUMS-induced inflammatory cytokines (caspase-1 and IL-1β) and apoptosis in hippocampus (30). And CUMS-induced the down-regulated BDNF and the activation of NLRP3 inflammasome in hippocampus or cortex could be both reversed in neuroligin3 (NLGN3) knockout mice (31).…”

Section: Discussionmentioning

confidence: 99%

Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation

Liang

et al. 2019

Front. Psychiatry

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The long-lasting loss of sleep is a generally acknowledged risk factor for the occurrence of major depressive disorder (MDD), whereas sleep abnormalities being a key clinic symptom of the MDD. In our previous work, we demonstrated that the sleep deprivation (SD) stimulates activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasomes as well as the release of IL-1β and IL-18 from astrocytes. However, the underlying mechanism connecting SD and MDD still requires further study. Apart of the secretion of the pro-inflammatory cytokines, SD affects production of brain-derived neurotrophic factor (BDNF) while release of BDNF from astrocytes appears a key contributor to mood disorders. If and how the activation of NLRP3 inflammasome following SD affects the level of BDNF remains unknown. Antidepressant fluoxetine acts through astroglial 5-hydroxytryptamine receptor 2B (5-HT2B); these receptors are also related to the sleep-wake cycle. Contribution of leptin to MDD has been discovered recently, although the mechanistic links between leptin and the depressive-like behaviors has not been revealed. In this study, we discovered: (i) that activation of NLRP3 inflammasome was involved in the depressive-like behaviors induced by SD; (ii) decrease in BDNF following SD required the activation of NLRP3 inflammasomes; (iii) leptin augmented the anti-depressive action of fluoxetine through an increase in expression of astrocytic 5-HT2B receptors. We suggest that decrease in BDNF by the activated NLRP3 inflammasomes in astrocytes is the key pathological event of the depressive-like behaviors induced by SD, while the combined treatment with fluoxetine and leptin improves therapeutic outcome for the depression induced by SD.

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Section: Discussionmentioning

confidence: 99%

Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation

Liang

et al. 2019

Front. Psychiatry

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“…An increase in vesicular GABA transmission may have aided recovery of olfactory bulb olfaction 15 . However, weight loss increased with the duration of DEP exposure; such exposure may have been accompanied by stress-induced depressive behavior 32 .…”

Section: Discussionmentioning

confidence: 99%

Neuronal and perineuronal changes of cerebral cortex after exposure to inhaled particulate matter

Kim

Lee

Park

et al. 2019

Sci Rep

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The inhalation of particulate matter (PM) increases the perineuronal nets (PNNs) in the cerebral cortex; however, little is known about the related molecular changes. We explored how PM exposure impacted cognitive function and the levels of PNN-related genes. BALB/c mice (6-week-old females, n = 32) were exposed to 1–5-μm diesel-extracted particles (DEPs) (100 µg/m3, 5 hours per day, 5 days per week) and categorized into the following four groups: 1) 4-week DEP exposure (n = 8); 2) 4-week control (n = 8); 3) 8-week DEP exposure (n = 8); and 4) 8-week control (n = 8). The Y-maze test and olfactory function test were conducted after 4 and 8 weeks of DEP exposure. The prefrontal cortex, olfactory bulb and temporal cortex were harvested from the animals in each group. The expression of genes related to PNNs (Tenascin C, matrix metalloproteinase [MMP]14, MMP9) and synaptic vesicular transporters of vesicular glutamergic transporter 1 (VGLUT1), VGLUT2, vesicular GABAergic transporter (VGAT) were measured. The temporal cortex was immunostained for neurocan, VGLUT1, and VGAT. The 4-week DEP group had lower total arm entry in the Y-maze test and olfactory sensitivity. These impaired behavioral functions recovered in the 8-week DEP group. Expression of tenascin C and MMP9 were increased in the cerebral cortex in the 8-week DEP group compared with the control group. The levels of VGLUT1, VGLUT2, and VGAT were elevated in the cerebral cortex of the 8-week DEP group compared with the control group. In immunostaining of the temporal cortex, the expression of neurocan, VGLUT1, and GAD67 were increased in the 8-week DEP group compared with the control group. The 4-week DEP inhalation impaired spatial activities and olfactory sensitivities. After 8 weeks of DEP exposure, the PNN components and their proteolytic enzymes and the vesicular transporters increased in the cerebral cortex.

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“…Such responses are, in part, due to environmental risk factors which then produce a neuroprogression of events resulting in the development of depression-like behaviors [4][5][6]. Results from clinical reports have shown that inflammation is closely associated with the pathogenesis of depression, as indicated by elevated levels of proinflammatory cytokines found in the peripheral circulation and some brain regions of depressed patients [7,8]. Postmortem studies have revealed that major depression patients exhibit a reduced size in pyramidal neurons and a decreased number of GABAergic interneurons [9].…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside-Rg1 Rescues Stress-Induced Depression-Like Behaviors via Suppression of Oxidative Stress and Neural Inflammation in Rats

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Depression is an inflammatory-related condition, with the progression in neuronal damage resulting in major depression disorder. Ginsenoside-Rg1, a sterol extract from the herb Panax ginseng, has been shown to exert neuroprotective effects upon neurodegeneration disorders. However, whether ginsenoside-Rg1 confers antidepressant-like effects on neuroinflammation as associated with depression, as well as the possible mechanism involved in these neuroprotective effects, is currently unclear. In the present report, we show that treatment with ginsenoside-Rg1 (40 mg/kg, i.p.) significantly ameliorated depressive-like behaviors as induced by chronic unpredictable mild stress (CUMS) in a rat model of depression. Moreover, these CUMS rats treated with ginsenoside-Rg1 showed reductions in the levels of the oxidative stress products and the activity in the antioxidant stress kinase. Furthermore, CUMS rats treated with ginsenoside-Rg1 showed ameliorated neuroinflammation and associated neuronal apoptosis along with a reduction in dendritic spine atrophy and display of depressive behaviors. Taken together, the results of this study suggest that ginsenoside-Rg1 produces antidepressant-like effects in CUMS-exposed rats; and one of the mechanisms for these antidepressant-like effects of ginsenoside-Rg1 appears to involve protection against oxidative stress and thus the neuronal deterioration resulting from inflammatory responses. These findings provide evidence for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related depression.

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Suppression of NLRP3 inflammasome attenuates stress-induced depression-like behavior in NLGN3-deficient mice

Cited by 42 publications

References 33 publications

Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation

Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation

Neuronal and perineuronal changes of cerebral cortex after exposure to inhaled particulate matter

Ginsenoside-Rg1 Rescues Stress-Induced Depression-Like Behaviors via Suppression of Oxidative Stress and Neural Inflammation in Rats

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