Abstract:
BACKGROUND:Recent work has established that Parkinson's disease (PD) patients have an altered gut microbiome, along with signs of intestinal inflammation. This could help explain the high degree of gastric disturbances in PD patients, as well as potentially be linked to the migration of peripheral inflammatory factors into the brain. To our knowledge, this is the first study to examine microbiome alteration prior to the induction of a PD murine model. METHODS:We presently assessed whether pre-treatment with the probiotic, VSL #3, or the inflammatory inducer, dextran sodium sulphate (DSS), would influence the PD-like pathology provoked by a dual hit toxin model using lipopolysaccharide (LPS) and paraquat exposure. RESULTS:While VSL #3 has been reported to have anti-inflammatory effects, DSS is often used as a model of colitis because of the gut inflammation and the breach of the intestinal barrier that it induces. We found that VSL#3 did not have any significant effects (beyond a blunting of LPS paraquat-induced weight loss). However, the DSS treatment caused marked changes in the gut microbiome and was also associated with augmented behavioral and inflammatory outcomes. In fact, DSS markedly increased taxa belonging to the Bacteroidaceae and Porphyromonadaceae families but reduced those from Rikencellaceae and S24-7, as well as provoking colonic pro-inflammatory cytokine expression, consistent with an inflamed gut. The DSS also increased the impact of LPS plus paraquat upon microglial morphology, along with circulating lipocalin-2 (neutrophil marker) and IL-6. Yet, neither DSS nor VSL#3 influenced the loss of substantia nigra dopamine neurons or the astrocytic and cytoskeleton remodeling protein changes that were provoked by the LPS followed by paraquat treatment. CONCLUSIONS:These data suggest that disruption of the intestinal integrity and the associated microbiome can interact with systemic inflammatory events to promote widespread brain-gut changes that could be relevant for PD and at the very least, suggestive of novel neuro-immune communication.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Dwyer Z,Chaiquin M,Landrigan J,Ayoub K,Shail P,Rocha J,Childers CL,Storey KB,Philpott DJ,Sun H,Hayley Sdoi
10.1186/s12974-020-02062-2subject
Has Abstractpub_date
2021-01-09 00:00:00pages
20issue
1issn
1742-2094pii
10.1186/s12974-020-02062-2journal_volume
18pub_type
杂志文章abstract:BACKGROUND:Transforming growth factor β (TGF-β) is a cytokine having multiple functions in the central nervous system such as promoting repair mechanisms in degenerative diseases and stroke. To date, however, its neuroprotective effects in non-disease conditions have not been studied METHODS:With the aim of exploring ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-42
更新日期:2012-02-28 00:00:00
abstract:BACKGROUND:Administration of exogenous interferon-γ (IFNγ) aggravates the symptoms of multiple sclerosis (MS), whereas interferon-β (IFNβ) is used for treatment of MS patients. We previously demonstrated that IFNγ induces apoptosis of oligodendroglial progenitor cells (OPCs), suggesting that IFNγ is more toxic to OPCs ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-8
更新日期:2011-01-24 00:00:00
abstract:BACKGROUND:Parkinson's disease (PD) is a neurodegenerative disease with characteristics and symptoms that are well defined. Nevertheless, its aetiology remains unknown. PD is characterized by the presence of Lewy bodies inside neurons. α-Synuclein (α-syn) is a soluble protein present in the pre-synaptic terminal of neu...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0412-7
更新日期:2015-10-26 00:00:00
abstract:BACKGROUND:The peroxisome proliferator-activated receptor (PPAR)-α activator, 5,8,11,14-eicosatetraynoic acid (ETYA), is an arachidonic acid analog. It is reported to inhibit up-regulation of pro-inflammatory genes; however, its underlying mechanism of action is largely unknown. In the present study, we focused on the ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-34
更新日期:2012-02-18 00:00:00
abstract:BACKGROUND:Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system that preferentially affects the optic nerves, spinal cord, and area postrema. A series of evidence suggested that B cells play a fundamental role in the pathogenesis of NMOSD. However, there are...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0961-z
更新日期:2017-09-25 00:00:00
abstract:BACKGROUND:Neurogenic inflammation is orchestrated by a large number of neuropeptides. Tachykinins (substance P, neurokinin A and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases. Autoimmunity may have a role in the pathogenesis of autism in ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-180
更新日期:2011-12-21 00:00:00
abstract:BACKGROUND:Since HIV-associated neurocognitive disorders (HANDs) occur in up to half of HIV-positive individuals, even with combined antiretroviral therapy (cART), adjunctive therapies are needed. Chronic CNS inflammation contributes to HAND and HIV encephalitis (HIVE). Baricitinib is a JAK 1/2 inhibitor approved in th...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1565-6
更新日期:2019-09-27 00:00:00
abstract:BACKGROUND:Spinal cord ischemia-reperfusion (I/R) involves two-phase injury, including an initial acute ischemic insult and subsequent inflammatory reperfusion injury, resulting in blood-spinal cord barrier (BSCB) dysfunction involving the TLR₄ pathway. However, the correlation between TLR₄/MyD₈₈-dependent and TLR₄/TRI...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-62
更新日期:2014-03-28 00:00:00
abstract::An amendment to this paper has been published and can be accessed via the original article. ...
journal_title:Journal of neuroinflammation
pub_type: 已发布勘误
doi:10.1186/s12974-020-01990-3
更新日期:2020-11-24 00:00:00
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 t...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0539-1
更新日期:2016-04-05 00:00:00
abstract:BACKGROUND:Complement activation via the lectin activation pathway (LP) has been identified as the key mechanism behind post-ischemic tissue inflammation causing ischemia-reperfusion injury (IRI) which can significantly impact the clinical outcome of ischemic disease. This work defines the contributions of each of the ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0684-6
更新日期:2016-08-30 00:00:00
abstract:BACKGROUND:A dose-limiting side effect of chemotherapeutic agents such as vincristine (VCR) is neuropathic pain, which is poorly managed at present. Chemokine-mediated immune cell/neuron communication in preclinical VCR-induced pain forms an intriguing basis for the development of analgesics. In a murine VCR model, CX3...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1116-6
更新日期:2018-04-06 00:00:00
abstract:BACKGROUND AND PURPOSE:Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) comb...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1368-1
更新日期:2018-11-30 00:00:00
abstract:BACKGROUND:Immune activation, specifically activation of macrophages and resident microglia, leading to inflammation is a key component in the progression of spinal cord injury (SCI). Macrophages/microglia exist in two states-the classically activated M1 phenotype that confers pro-inflammatory effects or the alternativ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1183-8
更新日期:2018-05-22 00:00:00
abstract:BACKGROUND:There are reasons to expect an association with Alzheimer's disease (AD) within the HLA region. The HLA-B & C genes have, however, been relatively understudied. A geographically specific association with HLA-B7 & HLA-Cw*0702 had been suggested by our previous, small study. METHODS:We studied the HLA-B & C a...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-3-33
更新日期:2006-12-18 00:00:00
abstract:BACKGROUND:Current evidence suggests a role of neuroinflammation in the pathogenesis of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of basal ganglia injury. Reportedly, nonsteroidal anti-inflammatory drugs (NSAIDs) mitigate DAergic neurotoxicity in rodent models of PD. ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-7-83
更新日期:2010-11-23 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by the deposition of extracellular fibrillar amyloid β (fΑβ) and the intracellular accumulation of neurofibrillary tangles. As AD progresses, Aβ drives a robust and prolonged inflammatory response via its recognition by micr...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1473-9
更新日期:2019-04-16 00:00:00
abstract:BACKGROUND:Adult human mesenchymal stem/stromal cells (hMSCs) from bone marrow have been reported to exhibit beneficial effects on spinal cord injury (SCI). A neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP) is known to decrease neuronal cell death and inflammatory response after ischemia, SCI, ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0252-5
更新日期:2015-02-22 00:00:00
abstract:BACKGROUND:Brain microvascular pericytes are important constituents of the neurovascular unit. These cells are physically the closest cells to the microvascular endothelial cells in brain capillaries. They significantly contribute to the induction and maintenance of the barrier functions of the blood-brain barrier. How...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-139
更新日期:2011-10-13 00:00:00
abstract:OBJECTIVES:The neurological basis for autism is still not fully understood, and the role of the interaction between neuro-inflammation and neurotransmission impairment needs to be clearer. This study aims to test the possible association between impaired levels of gamma aminobutyric acid (GABA), serotonin, dopamine, ox...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-4
更新日期:2014-01-08 00:00:00
abstract:BACKGROUND:In brain tissues from multiple sclerosis (MS) patients, clusters of activated HLA-DR-expressing microglia, also referred to as preactive lesions, are located throughout the normal-appearing white matter. The aim of this study was to gain more insight into the frequency, distribution and cellular architecture...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-156
更新日期:2012-07-02 00:00:00
abstract:AIM:To determine whether Compound 49b, a novel beta-adrenergic receptor agonist, can prevent increased inflammation and apoptosis in mice after exposure to ocular blast. METHODS:Eyes of C57/BL6 mice were exposed to a blast of air from a paintball gun at 26 psi (≈0.18 MPa). Eyes were collected 4 hours, 24 hours, and 72...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-10-96
更新日期:2013-07-30 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:In brain inflammatory diseases, axonal damage is one of the most critical steps in the cascade that leads to permanent disability. Thus, identifying the initial events triggered by inflammation or oxidative stress that provoke axonal damage is critical for the development of neuroprotective therapies. Energy...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0375-8
更新日期:2015-08-28 00:00:00
abstract:BACKGROUND:The small population of glioma stem-like cells (GSCs) contributes to tumor initiation, malignancy, and recurrence in glioblastoma. However, the maintenance of GSC properties in the tumor microenvironment remains unclear. In glioma, non-neoplastic cells create an inflammatory environment and subsequently medi...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1535-z
更新日期:2019-07-12 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...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1201-x
更新日期:2018-06-09 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:Synucleinopathies comprise a group of neurodegenerative diseases associated with abnormal accumulation of α-synuclein. One of the key factors that contribute to the progression of synucleinopathies is neuroinflammation. However, the role of lymphocytes in synucleinopathies like Parkinson's disease (PD) remai...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0632-5
更新日期:2016-06-30 00:00:00
abstract:BACKGROUND:Chronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity i...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0889-3
更新日期:2017-06-08 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