Abstract:
BACKGROUND:The NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3) is an intracellular protein complex that plays an important role in innate immune sensing. Its activation leads to the maturation of caspase-1 and regulates the cleavage of interleukin (IL)-1β and IL-18. Various studies have shown that activation of the immune system plays a pivotal role in the development of fatigue. However, the mechanisms underlying the association between immune activation and fatigue remained elusive, and few reports have described the involvement of NLRP3 inflammasome activation in fatigue. METHODS:We established a mouse fatigue model with lipopolysaccharide (LPS, 3 mg/kg) challenge combined with swim stress. Both behavioural and biochemical parameters were measured to illustrate the characteristics of this model. We also assessed NLRP3 inflammasome activation in the mouse diencephalon, which is the brain region that has been suggested to be responsible for fatigue sensation. To further identify the role of NLRP3 inflammasome activation in the pathogenesis of chronic fatigue syndrome (CFS), NLRP3 KO mice were also subjected to LPS treatment and swim stress, and the same parameters were evaluated. RESULTS:Mice challenged with LPS and subjected to the swim stress test showed decreased locomotor activity, decreased fall-off time in a rota-rod test and increased serum levels of IL-1β and IL-6 compared with untreated mice. Serum levels of lactic acid and malondialdehyde (MDA) were not significantly altered in the treated mice. We demonstrated increased NLRP3 expression, IL-1β production and caspase-1 activation in the diencephalons of the treated mice. In NLRP3 KO mice, we found remarkably increased locomotor activity with longer fall-off times and decreased serum IL-1β levels compared with those of wild-type (WT) mice after LPS challenge and the swim stress test. IL-1β levels in the diencephalon were also significantly decreased in the NLRP3 KO mice. By contrast, IL-6 levels were not significantly altered. CONCLUSIONS:These findings suggest that LPS-induced fatigue is an IL-1β-dependent process and that the NLRP3/caspase-1 pathway is involved in the mechanisms of LPS-induced fatigue behaviours. NLRP3/caspase-1 inhibition may be a promising therapy for fatigue treatment.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Zhang ZT,Du XM,Ma XJ,Zong Y,Chen JK,Yu CL,Liu YG,Chen YC,Zhao LJ,Lu GCdoi
10.1186/s12974-016-0539-1subject
Has Abstractpub_date
2016-04-05 00:00:00pages
71issue
1issn
1742-2094pii
10.1186/s12974-016-0539-1journal_volume
13pub_type
杂志文章abstract:BACKGROUND:The proteasome is a multisubunit enzyme complex involved in protein degradation, which is essential for many cellular processes. During inflammation, the constitutive subunits are replaced by their inducible counterparts, resulting in the formation of the immunoproteasome. METHODS:We investigated the expres...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0662-z
更新日期:2016-08-26 00:00:00
abstract:BACKGROUND:Necrotizing enterocolitis (NEC) is an acute gut inflammatory disorder that occurs in preterm infants in the first weeks after birth. Infants surviving NEC often show impaired neurodevelopment. The mechanisms linking NEC lesions with later neurodevelopment are poorly understood but may include proinflammatory...
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更新日期:2018-06-09 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive abilities and memory leading to dementia. Electroacupuncture (EA) is a complementary alternative medicine approach, applying an electrical current to acupuncture points. In clinical and animal studies, EA ...
journal_title:Journal of neuroinflammation
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更新日期:2019-12-13 00:00:00
abstract:BACKGROUND:Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SN) while neighboring ventral tegmental area (VTA) DA neurons are relatively spared. Mechanisms underlying the selective protection of the VTA and susceptibility of the SN a...
journal_title:Journal of neuroinflammation
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doi:10.1186/s12974-018-1181-x
更新日期:2018-05-11 00:00:00
abstract:BACKGROUND:Patients diagnosed with chronic fatigue syndrome (CFS) or fibromyalgia experience chronic pain. Concomitantly, the rat model of CFS exhibits microglial activation in the lumbar spinal cord and pain behavior without peripheral tissue damage and/or inflammation. The present study addressed the mechanism underl...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1456-x
更新日期:2019-03-30 00:00:00
abstract:BACKGROUND:In sepsis syndromes the severity of the inflammation triggers microvascular dysfunction and early organ failure. We studied the effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculatory integrity in an endotoxinemic rat model. METHODS:In both control and endotoxinemic (5 mg/kg li...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-183
更新日期:2012-07-25 00:00:00
abstract:BACKGROUND:Traumatic brain injury (TBI) is a devastating neurological condition and a frequent cause of permanent disability. Posttraumatic inflammation and brain edema formation, two pathological key events contributing to secondary brain injury, are mediated by the contact-kinin system. Activation of this pathway in ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0815-8
更新日期:2017-02-20 00:00:00
abstract:BACKGROUND:Traumatic brain injury (TBI) results in long-term neurological deficits, which may be mediated in part by pro-inflammatory responses in both the injured brain and the circulation. Inflammation may be involved in the subsequent development of neurodegenerative diseases and post-injury seizures. The p75 neurot...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0544-4
更新日期:2016-04-22 00:00:00
abstract:BACKGROUND AND PURPOSE:Regulation of neural inflammation is considered as a vital therapeutic target in ischemic stroke. All-trans retinoic acid (atRA), a potent immune modulator, has raised interest in the field of stroke therapy. However, the immunological mechanisms for atRA-mediated neuroprotection remain elusive. ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1557-6
更新日期:2019-08-31 00:00:00
abstract:BACKGROUND:Glia-mediated neuroinflammation is related to brain injury exacerbation after cerebral ischemia/reperfusion (I/R) injury. Astrocytic hemichannels or gap junctions, which were mainly formed by connexin-43, have been implicated in I/R damage. However, the exact roles of astrocytic hemichannels and gap junction...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1127-3
更新日期:2018-03-27 00:00:00
abstract:BACKGROUND:Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we ev...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-23
更新日期:2011-03-09 00:00:00
abstract:BACKGROUND:The mechanism of leukocyte transendothelial migration (TEM) across the highly restrictive blood-brain barrier (BBB) remains enigmatic, with paracellular TEM thought to require leukocytes to somehow navigate the obstructive endothelial tight junctions (TJs). Transient interactions between TJ proteins on the r...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0755-8
更新日期:2016-11-16 00:00:00
abstract:BACKGROUND:Maternal obesity as a result of high levels of saturated fat (HFD) consumption leads to significant negative health outcomes in both mother and exposed offspring. Offspring exposed to maternal HFD show sex-specific alterations in metabolic, behavioral, and endocrine function, as well as increased levels of b...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01798-1
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:This study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats. METHODS:Expression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-1037-9
更新日期:2018-01-04 00:00:00
abstract::Chronic inflammation has been shown to contribute to the development of a wide variety of disorders by means of a number of proposed mechanisms. Depression and cognitive impairment are two such disorders which may share a closely linked inflammatory etiology. The ability of inflammatory mediators to alter the activity...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
doi:10.1186/s12974-014-0151-1
更新日期:2014-09-02 00:00:00
abstract:BACKGROUND:Interleukin-1 beta converting enzyme (ICE, caspase 1) is a cysteine protease that processes immature pro-IL-1β into active mature IL-1β. IL-1β is a pro-inflammatory cytokine that mediates many of the physiological and behavioral responses to inflammation. Genetic deletion of ICE has previously been shown to ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-10-54
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:Glaucoma is a complex neurodegeneration and a leading cause of blindness worldwide. Current therapeutic strategies, which are all directed towards lowering the intraocular pressure (IOP), do not stop progression of the disease. We have demonstrated that recombinant adeno-associated virus (rAAV) gene delivery...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0499-5
更新日期:2016-02-15 00:00:00
abstract:BACKGROUND:Meningothelial cells (MECs) are the cellular components of the meninges. As such, they provide important barrier function for the central nervous system (CNS) building the interface between neuronal tissue and the cerebrospinal fluid (CSF), and are also part of the immune response of the CNS. METHODS:Human,...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-35
更新日期:2014-02-24 00:00:00
abstract:BACKGROUND:Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). However, this physiological mechanism has multiple manifestations that range from impaired clearance of unfolded proteins to altered mitochondrial dynamics and apoptosis. While connections between t...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0788-z
更新日期:2017-01-23 00:00:00
abstract:BACKGROUND:Cyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01804-6
更新日期:2020-05-02 00:00:00
abstract:BACKGROUND:Extracellular matrix (ECM) proteins play critical functions regulating vascular formation and function. Laminin is a major component of the vascular basal lamina, and transgenic mice deficient in astrocyte or pericyte laminin show defective blood-brain barrier (BBB) integrity, indicating an important instruc...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0987-2
更新日期:2017-11-09 00:00:00
abstract:BACKGROUND:Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1beta is primarily neurotoxic in ischemic stroke, TNF-alpha may have neurotoxic and/or neuroprotective effects. We investigated whether IL-1be...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-5-46
更新日期:2008-10-23 00:00:00
abstract:BACKGROUND:Each year in the USA, over 2.4 million people experience mild traumatic brain injury (TBI), which can induce long-term neurological deficits. The dentate gyrus of the hippocampus is notably susceptible to damage following TBI, as hilar mossy cell changes in particular may contribute to post-TBI dysfunction. ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-1720-0
更新日期:2020-01-31 00:00:00
abstract:BACKGROUND:Brain inflammation including increases in inflammatory cytokines such as IL-1β is widely believed to contribute to the pathophysiology of Alzheimer's disease. Although IL-1β-induced impairments in long-term potentiation (LTP) in acute hippocampal slices and memory functions in vivo have been well documented,...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1158-9
更新日期:2018-04-30 00:00:00
abstract:BACKGROUND:Conditions of inflammatory tissue distress are associated with high extracellular levels of adenosine, due to increased adenosine triphosphate (ATP) degradation upon cellular stress or the release of extracellular ATP upon cell death, which can be degraded to adenosine by membrane-bound ecto-enzymes like CD3...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0512-z
更新日期:2016-02-26 00:00:00
abstract:BACKGROUND:Opioid receptors are known to control neurotransmission of various peptidergic neurons, but their potential role in regulation of microglia and neuronal cell communications is unknown. We investigated the role of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) on microglia in the regulation of apo...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0844-3
更新日期:2017-04-14 00:00:00
abstract:OBJECTIVE:Febrile seizures are the most common form of childhood seizures. Fever is induced by pro-inflammatory cytokines during infection, and pro-inflammatory cytokines may trigger the development of febrile seizures. In order to determine whether active inflammation, including high mobility group box-1 (HMGB1) and p...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-135
更新日期:2011-10-11 00:00:00
abstract:BACKGROUND:This study investigated whether therapeutic hypercapnia (TH) ameliorated blood-brain barrier (BBB) damage and improved the neurologic outcome in a rat model of lateral fluid percussion injury (FPI), and explored the possible underlying mechanism. METHODS:Rats underwent lateral FPI and received inhalation of...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1427-2
更新日期:2019-02-13 00:00:00
abstract:BACKGROUND:Betaine (glycine betaine or trimethylglycine) plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well kno...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-153
更新日期:2011-11-04 00:00:00
abstract::Nerve injury-induced chronic pain has been an urgent problem for both public health and clinical practice. While transition to chronic pain is not an inevitable consequence of nerve injuries, the susceptibility/resilience factors and mechanisms for chronic neuropathic pain after nerve injuries still remain unknown. Cu...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
doi:10.1186/s12974-019-1684-0
更新日期:2020-01-03 00:00:00