Abstract:
BACKGROUND:The cellular prion protein (PrPC) is an evolutionary conserved protein abundantly expressed not only in the central nervous system but also peripherally including the immune system. A line of Norwegian dairy goats naturally devoid of PrPC (PRNP Ter/Ter) provides a novel model for studying PrPC physiology. METHODS:In order to explore putative roles for PrPC in acute inflammatory responses, we performed a lipopolysaccharide (LPS, Escherichia coli O26:B6) challenge of 16 goats (8 PRNP +/+ and 8 PRNP Ter/Ter) and included 10 saline-treated controls (5 of each PRNP genotype). Clinical examinations were performed continuously, and blood samples were collected throughout the trial. Genome-wide transcription profiles of the choroid plexus, which is at the blood-brain interface, and the hippocampus were analyzed by RNA sequencing, and the same tissues were histologically evaluated. RESULTS:All LPS-treated goats displayed clinical signs of sickness behavior, which were of significantly (p < 0.01) longer duration in animals without PrPC. In the choroid plexus, a substantial alteration of the transcriptome and activation of Iba1-positive cells were observed. This response included genotype-dependent differential expression of several genes associated with the immune response, such as ISG15, CXCL12, CXCL14, and acute phase proteins, among others. Activation of cytokine-responsive genes was skewed towards a more profound type I interferon response, and a less obvious type II response, in PrPC-deficient goats. The magnitude of gene expression in response to LPS was smaller in the hippocampus than in the choroid plexus. Resting state expression profiles revealed a few differences between the PRNP genotypes. CONCLUSIONS:Our data suggest that PrPC acts as a modulator of certain pathways of innate immunity signaling, particularly downstream of interferons, and probably contributes to protection of vulnerable tissues against inflammatory damage.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Salvesen Ø,Reiten MR,Espenes A,Bakkebø MK,Tranulis MA,Ersdal Cdoi
10.1186/s12974-017-0879-5subject
Has Abstractpub_date
2017-05-22 00:00:00pages
106issue
1issn
1742-2094pii
10.1186/s12974-017-0879-5journal_volume
14pub_type
杂志文章abstract::Opioid therapies for chronic pain are undermined by many adverse side effects that reduce their efficacy and lead to dependence, abuse, reduced quality of life, and even death. We have recently reported that sphingosine-1-phosphate (S1P) 1 receptor (S1PR1) antagonists block the development of morphine-induced hyperalg...
journal_title:Journal of neuroinflammation
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doi:10.1186/s12974-020-01975-2
更新日期:2020-10-22 00:00:00
abstract:BACKGROUND:Cannabinoid-2 receptor (CB2R) plays an important role in the cascading inflammation following ischemic injury. The toll-like receptors 4 (TLR4)/matrix metalloproteinase 9 (MMP9) signal pathway is involved in blood-brain barrier dysfunction induced by ischemia stroke. The aim of this study is to investigate t...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01784-7
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0996-1
更新日期:2017-11-16 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
pub_type: 杂志文章
doi:10.1186/s12974-019-1665-3
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1689-8
更新日期:2020-01-27 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV) continues to be one of the most prevalent global health afflictions to date. The advent and introduction of combined antiretroviral therapy (cART) has made a significant impact on the course of infection. However, as patients are living longer, many HIV-associated illnesses ar...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
doi:10.1186/1742-2094-10-144
更新日期:2013-12-01 00:00:00
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 ...
journal_title:Journal of neuroinflammation
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doi:10.1186/s12974-020-02062-2
更新日期:2021-01-09 00:00:00
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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:Therapeutic modalities effective in patients with progressive forms of multiple sclerosis (MS) are limited. In a murine model of progressive MS, the sustained disability during the chronic phase of experimental autoimmune encephalomyelitis (EAE) correlated with elevated expression of interleukin (IL)-6, a cy...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0293-9
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-4-31
更新日期:2007-12-20 00:00:00
abstract:BACKGROUND:The prognosis of bacterial meningitis largely depends on the severity of the inflammatory response. The transcription factor CAAT/enhancer-binding protein δ (C/EBPδ) plays a key role in the regulation of the inflammatory response during bacterial infections. Consequently, we assessed the role of C/EBPδ durin...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0309-5
更新日期:2015-05-10 00:00:00
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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: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::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
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章,多中心研究
doi:10.1186/1742-2094-11-101
更新日期:2014-06-10 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01788-3
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0930-6
更新日期:2017-08-04 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0352-2
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-96
更新日期:2014-05-27 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
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1676-0
更新日期:2020-02-19 00:00:00
abstract::Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
doi:10.1186/1742-2094-10-43
更新日期:2013-04-01 00:00:00
abstract:BACKGROUND:Amyloid β (Aβ)-induced vascular dysfunction significantly contributes to the pathogenesis of Alzheimer's disease (AD). Aβ is known to impair endothelial nitric oxide synthase (eNOS) activity, thus inhibiting endothelial nitric oxide production (NO). METHOD:In this study, we investigated Aβ-effects on heat s...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0304-x
更新日期:2015-05-03 00:00:00
abstract:BACKGROUND:Changes in the gene expressions for tumor necrosis factor-α (TNF-α) and/or interleukin-1β (IL-1β) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-α, IL-1β, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-30
更新日期:2011-04-09 00:00:00
abstract:AIM:Pre-clinical studies in models of multiple sclerosis and other inflammatory disorders suggest that high-salt diet may induce activation of the immune system and potentiate inflammation. However, high-salt diet constitutes a common non-pharmacological intervention to treat autonomic problems in synucleinopathies suc...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-1714-y
更新日期:2020-01-24 00:00:00
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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:The chemokine interleukin-8 (IL-8) and its receptor CXCR2 contribute to chemotactic responses in Alzheimer's disease (AD); however, properties of the ligand and receptor have not been characterized in animal models of disease. The primary aim of our study was to examine effects of pharmacological antagonism ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0339-z
更新日期:2015-08-09 00:00:00
abstract:BACKGROUND:The family of 14-3-3 proteins plays an important role in the regulation of cell survival and death. Here, we investigate the role of the 14-3-3 gamma (14-3-3 γ) subunit for glial responses in autoimmune demyelination. METHODS:Expression of 14-3-3 γ in glial cell culture was investigated by reverse transcrip...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0381-x
更新日期:2015-10-06 00:00:00