Abstract:
BACKGROUND:Increased tryptophan metabolism towards the production of kynurenine via indoleamine/tryptophan-2,3-dioxygenases (DOs: Ido1, Ido2, and Tdo2) is strongly associated with the prevalence of major depressive disorder in patients and the induction of depression-like behaviors in animal models. Several studies have suggested that activation of the immune system or elevated corticosteroids drive DO expression; however, mechanisms linking cytokines, corticosteroids, and DOs to psychiatric diseases remain unclear. Various attempts have been made to correlate DO gene expression within the brain to behavior, but disparate results have been obtained. We believe that discrepancies arise as a result of the under-recognized existence of multiple mRNA transcripts for each DO. Unfortunately, there are no reports regarding how the multiple transcripts are distributed or regulated. Here, we used organotypic hippocampal slice cultures (OHSCs) to directly test the ability of inflammatory and stress mediators to differentially regulate DO transcripts. METHODS:OHSCs were treated with pro-inflammatory mediators (interferon-gamma (IFNγ), lipopolysaccharide (LPS), and polyinosine-polycytidylic acid (pI:C)) with or without corticosteroids (dexamethasone (Dex: glucocorticoid receptor (GR) agonist), aldosterone (Aldo: mineralocorticoid receptor (MR) agonist), or corticosterone (Cort: GR/MR agonist)). RESULTS:IFNγ induced Ido1-full length (FL) and Ido1-variant (v) expression, and surprisingly, Dex, Cort, and Aldo interacted with IFNγ to further elevate expression of Ido1, importantly, in a transcript dependent manner. IFNγ, LPS, and pI:C increased expression of Ido2-v1 and Ido2-v3 transcripts, whereas only IFNγ increased expression of Ido2-v2. Overall Ido2 transcripts were relatively unaffected by GR or MR activation. Naïve mouse brain expresses multiple Tdo2 transcripts. Dex and Cort induced expression of only one of the three Tdo2 transcripts (Tdo2-FL) in OHSCs. CONCLUSIONS:These results establish that multiple transcripts for all three DOs are expressed within the mouse hippocampus, under the control of distinct regulatory pathways. These data identify a previously unrecognized interaction between corticosteroid receptor activation and inflammatory signals on DO gene expression, which suggest that corticosteroids act to differentially enhance gene expression of Ido1, Ido2, and Tdo2.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Brooks AK,Lawson MA,Smith RA,Janda TM,Kelley KW,McCusker RHdoi
10.1186/s12974-016-0563-1subject
Has Abstractpub_date
2016-05-03 00:00:00pages
98issue
1issn
1742-2094pii
10.1186/s12974-016-0563-1journal_volume
13pub_type
杂志文章abstract:BACKGROUND:Experimental autoimmune encephalomyelitis (EAE) is the most commonly used and clinically relevant murine model for human multiple sclerosis (MS), a demyelinating autoimmune disease characterized by mononuclear cell infiltration into the central nervous system (CNS). The aim of the present study was to apprai...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01936-9
更新日期:2020-09-07 00:00:00
abstract:BACKGROUND:Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147, basigin) is an inducer of the expression of several matrix metalloproteinases (MMPs). We reported previously that blocking EMMPRIN activity reduced neuroinflammation and severity of disease in an animal model of multiple sclerosis (MS), experime...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-64
更新日期:2012-04-05 00:00:00
abstract:BACKGROUND:Tumor necrosis factor-α (TNF-α) is an important inflammatory factor produced by activated macrophages and monocytes and plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). To evaluate the effect of TNF-α signaling suppression and the potential of TNF-α in the treatment of DPN...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-10-69
更新日期:2013-06-04 00:00:00
abstract:BACKGROUND:Demyelination and remyelination are common pathological processes in many neurological disorders, including multiple sclerosis (MS). Clinical evidence suggests extensive involvement of the thalamocortical (TC) system in patients suffering from MS. METHODS:Using murine brain slices of the primary auditory co...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0629-0
更新日期:2016-06-22 00:00:00
abstract:BACKGROUND:Parkinson's disease (PD) is frequently associated with gastrointestinal (GI) symptoms, including constipation and defecatory dysfunctions. The mechanisms underlying such disorders are still largely unknown, although the occurrence of a bowel inflammatory condition has been hypothesized. This study examined t...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0608-5
更新日期:2016-06-13 00:00:00
abstract:BACKGROUND:Cranial radiotherapy is used to treat tumors of the central nervous system (CNS), as well as non-neoplastic conditions such as arterio-venous malformations; however, its use is limited by the tolerance of adjacent normal CNS tissue, which can lead to devastating long-term sequelae for patients. Despite decad...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0496-8
更新日期:2016-02-03 00:00:00
abstract::BACKGROUND: Oligodendrocytes, neurons, astrocytes, microglia, and endothelial cells are capable of synthesizing complement inhibitor proteins. Oligodendrocytes are vulnerable to complement attack, which is particularly observed in multiple sclerosis. This vulnerability may be related to a deficiency in their ability t...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-1-17
更新日期:2004-08-24 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
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-57
更新日期:2011-05-24 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2015-01-15 00:00:00
abstract:BACKGROUND:It has recently become apparent that neuroinflammation may play a significant role in Parkinson's disease (PD). This is also the case in animal paradigms of the disease. The potential neuroprotective action of the glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 (EX-4), which is protective against...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-5-19
更新日期:2008-05-21 00:00:00
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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
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0295-7
更新日期:2015-05-22 00:00:00
abstract:BACKGROUND:Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. OBJECTIVE:We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addr...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-105
更新日期:2011-08-24 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:Chorioamnionitis is associated with an increased risk of brain injury in preterm neonates. Inflammatory changes in brain could underlie this injury. Here, we evaluated whether neuroinflammation is induced by chorioamnionitis in a clinically relevant model. METHODS:Rhesus macaque fetuses were exposed to eith...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0706-4
更新日期:2016-09-06 00:00:00
abstract:BACKGROUND:Multiple Sclerosis (MS) is characterized by the pathological trafficking of leukocytes into the central nervous system (CNS). Using the murine MS model, experimental autoimmune encephalomyelitis (EAE), we previously demonstrated that antagonism of the chemokine receptor CXCR7 blocks endothelial cell sequestr...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-170
更新日期:2011-12-06 00:00:00
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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
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-27
更新日期:2011-03-31 00:00:00
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journal_title:Journal of neuroinflammation
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更新日期:2015-12-15 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
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更新日期:2020-08-01 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0611-x
更新日期:2016-06-22 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0947-x
更新日期:2017-08-31 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1499-z
更新日期:2019-05-31 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1628-8
更新日期:2019-11-22 00:00:00
abstract:BACKGROUND:Both human and animal studies have shown beneficial effects of physical exercise on brain health but most tend to be based on aerobic rather than resistance type regimes. Resistance exercise has the advantage of improving both muscular and cardiovascular function, both of which can benefit the frail and the ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1653-7
更新日期:2020-01-03 00:00:00
abstract:BACKGROUND:Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized. OBJECTIVE:The objective of this study is to investigate whether...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0899-1
更新日期:2017-06-24 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0579-6
更新日期:2016-05-24 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:Some children with autism spectrum disorders (ASD) are characterized by fluctuating behavioral symptoms following immune insults, persistent gastrointestinal (GI) symptoms, and a lack of response to the first-line intervention measures. These children have been categorized as the ASD-inflammatory subtype (AS...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-014-0187-2
更新日期:2014-10-27 00:00:00