Abstract:
BACKGROUND:In schizophrenia, genetic background may provide a substrate for intrinsic maldevelopment of the brain through environmental influences, by recruiting neurotrophic factors and cytokines, to trigger the changes that lead to impaired neuronal functions. Cytokines being the key regulators of immune/inflammatory reactions are also known to influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. Therefore, functional polymorphisms in cytokine genes may result in imbalances in the pro- and anti-inflammatory cytokine production. METHODS:We screened polymorphisms in pro- and anti-inflammatory cytokine genes using a case-control association study in a South Indian population. The role of allele, genotype, haplotype, and diplotypes of these cytokine genes and their epistatic interactions were assessed in contributing to the risk of developing schizophrenia. Meta-analysis for the reported associations was also monitored for global significance. RESULTS:The pro-inflammatory cytokine gene polymorphisms in IL1Ars1800587, IL6rs1800796, TNFArs361525, and IFNGrs2069718 were associated with schizophrenia. The study also provides significant evidence for strong epistatic interactions among pro-inflammatory cytokine genes IL6 and IFNG in the development of schizophrenia. In silico analysis suggested that associated risk variants were indicative of altered transcriptional activity with higher production of IL1α, IL-6, TNF-α, and IFN-ɤ cytokines. Meta-analysis indicated heterogeneity among study population while IL1Ars1800587 was found to be globally significant. CONCLUSIONS:It is important to identify the nature of inflammatory response that can be amplified by the environment, to influence either Th1 response or Th2 response. The associated functional variants in the study are involved with increased expression resulting in higher production of the pro-inflammatory cytokines IL-1α, IL-6, TNF-α, and IFN-γ. The interaction of immunological stressors with these high producer alleles of pro-inflammatory cytokines may suggest that even a lower threshold may be sufficient to induce a resultant chronic effect on the psycho-social and environmental stressors that may result in the development and pathogenesis of schizophrenia. Understanding environmental factors that influence the expression of these pro-inflammatory cytokine genes or their interaction can possibly help in dissecting the phenotypic variation and therapeutic response to antipsychotics in schizophrenia.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Srinivas L,Vellichirammal NN,Alex AM,Nair C,Nair IV,Banerjee Mdoi
10.1186/s12974-016-0569-8subject
Has Abstractpub_date
2016-05-13 00:00:00pages
105issue
1issn
1742-2094pii
10.1186/s12974-016-0569-8journal_volume
13pub_type
杂志文章abstract:BACKGROUND:Traumatic brain injury (TBI) is a major cause of death and disability in the USA and the world; it constitutes 30% of injury-related deaths (Taylor et al., MMWR Surveill Summ 66:1-16, 2017). Contact sports athletes often experience repetitive TBI (rTBI), which exerts a cumulative effect later in life. Visual...
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
abstract:BACKGROUND:Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by gradual memory loss and neuropsychiatric symptoms. We have previously demonstrated that the 2-({3-[2-(1-cyclohexene-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanami...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-02022-w
更新日期:2020-11-22 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0475-0
更新日期:2016-01-12 00:00:00
abstract::Multiple sclerosis (MS) is thought to be a CD4+ T cell mediated autoimmune demyelinating disease of the central nervous system (CNS) that is rarely diagnosed during infancy. Cellular and molecular mechanisms that confer disease resistance in this age group are unknown. We tested the hypothesis that a differential comp...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-10-67
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abstract:BACKGROUND:In meningitis, the cerebrospinal fluid contains high levels of innate immune molecules (e.g. complement) which are essential to ward off the infectious challenge and to promote the infiltration of phagocytes (neutrophils, monocytes). However, epithelial cells of either the ependymal layer, one of the establi...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-3-22
更新日期:2006-09-02 00:00:00
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journal_title:Journal of neuroinflammation
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doi:10.1186/s12974-018-1342-y
更新日期:2018-11-06 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus type 1 (HIV-1) induces neuronal dysfunction through host cellular factors and viral proteins including viral protein R (Vpr) released from infected macrophages/microglia. Vpr is important for infection of terminally differentiated cells such as macrophages. The objective of this ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-138
更新日期:2012-06-22 00:00:00
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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
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0254-3
更新日期:2015-02-27 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0258-z
更新日期:2015-02-20 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0252-5
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0666-8
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0234-7
更新日期:2015-01-27 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1603-4
更新日期:2019-11-13 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0923-5
更新日期:2017-07-21 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
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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
abstract:BACKGROUND:Monocyte infiltration is involved in the pathogenesis of many retinal degenerative conditions. This process traditionally depends on local expression of chemokines, though the roles of many of these in the degenerating retina are unclear. Here, we investigate expression and in situ localization of the broad ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-014-0224-1
更新日期:2015-01-17 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1249-7
更新日期:2018-07-18 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0297-5
更新日期:2015-04-18 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease affecting the neuromuscular system. While there have been a number of important genetic discoveries, there are no therapeutics capable of stopping its insidious progression. Lessons from clinical histories reveal that ALS can start focally at a single...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
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更新日期:2020-06-06 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
doi:10.1186/s12974-019-1498-0
更新日期:2019-06-07 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:2018-01-22 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-014-0229-9
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abstract:BACKGROUND:HIV-infected individuals are at an increased risk of developing neurological abnormalities. HIV induces neurotoxicity by host cellular factors and individual viral proteins. Some of these proteins including viral protein R (Vpr) promote immune activation and neuronal damage. Vpr is known to contribute to cel...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-53
更新日期:2014-03-22 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1685-z
更新日期:2019-12-30 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0891-9
更新日期:2017-06-06 00:00:00
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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
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0347-z
更新日期:2015-07-02 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
doi:10.1186/s12974-020-01732-5
更新日期:2020-02-12 00:00:00