1
40
2
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1186/s12974-018-1100-1" target="_blank" rel="noreferrer noopener">http://doi.org/10.1186/s12974-018-1100-1</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
73-73
Issue
1
Volume
15
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
The glycoprotein GPNMB attenuates astrocyte inflammatory responses through the CD44 receptor.
Publisher
An entity responsible for making the resource available
Journal of neuroinflammation
Date
A point or period of time associated with an event in the lifecycle of the resource
2018
2018-03
Subject
The topic of the resource
Female; Humans; Male; Animals; Mice; Reactive Oxygen Species/metabolism; Astrocyte; CD44; GPNMB; *Neuroinflammation; *Parkinson's disease; Case-Control Studies; Analysis of Variance; Signal Transduction/drug effects; Hyaluronan Receptors/*metabolism; Glial Fibrillary Acidic Protein/metabolism; Nitric Oxide/metabolism; Cells; Cultured; RNA; Messenger/metabolism; Chemical; 3; Databases; 1-Methyl-4-phenyl-1; 2; 6-tetrahydropyridine/pharmacology; Anti-Inflammatory Agents/*therapeutic use; Astrocytes/*drug effects; Cytokines/genetics/metabolism; Inflammation/*drug therapy/etiology; Membrane Glycoproteins/*therapeutic use; Neurotoxins/toxicity; Parkinson Disease/complications/*pathology
Creator
An entity primarily responsible for making the resource
Neal Matthew L; Boyle Alexa M; Budge Kevin M; Safadi Fayez F; Richardson Jason R
Description
An account of the resource
BACKGROUND: Neuroinflammation is one of the hallmarks of neurodegenerative diseases, such as Parkinson's disease (PD). Activation of glial cells, including microglia and astrocytes, is a characteristic of the inflammatory response. Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that releases a soluble signaling peptide when cleaved by ADAM10 or other extracellular proteases. GPNMB has demonstrated a neuroprotective role in animal models of ALS and ischemia. However, the mechanism of this protection has not been well established. CD44 is a receptor expressed on astrocytes that can bind GPNMB, and CD44 activation has been demonstrated to reduce NFkappaB activation and subsequent inflammatory responses in macrophages. GPNMB signaling has not been investigated in models of PD or specifically in astrocytes. More recently, genetic studies have linked polymorphisms in GPNMB with risk for PD. Therefore, it is important to understand the role this signaling protein plays in PD. METHODS: We used data mining techniques to evaluate mRNA expression of GPNMB and its receptor CD44 in the substantia nigra of PD and control brains. Immunofluorescence and qPCR techniques were used to assess GPNMB and CD44 levels in mice treated with MPTP. In vitro experiments utilized the immortalized mouse astrocyte cell line IMA2.1 and purified primary mouse astrocytes. The effects of recombinant GPNMB on cytokine-induced astrocyte activation was determined by qPCR, immunofluorescence, and measurement of nitric oxide and reactive oxygen production. RESULTS: Increased GPNMB and CD44 expression was observed in the substantia nigra of human PD brains and in GFAP-positive astrocytes in an animal model of PD. GPNMB treatment attenuated cytokine-induced levels of inducible nitric oxide synthase, nitric oxide, reactive oxygen species, and the inflammatory cytokine IL-6 in an astrocyte cell line and primary mouse astrocytes. Using primary mouse astrocytes from CD44 knockout mice, we found that the anti-inflammatory effects of GPNMB are CD44-mediated. CONCLUSIONS: These results demonstrate that GPNMB may exert its neuroprotective effect through reducing astrocyte-mediated neuroinflammation in a CD44-dependent manner, providing novel mechanistic insight into the neuroprotective properties of GPNMB.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1186/s12974-018-1100-1" target="_blank" rel="noreferrer noopener">10.1186/s12974-018-1100-1</a>
*Neuroinflammation
*Parkinson's disease
1-Methyl-4-phenyl-1
2
2018
3
6-tetrahydropyridine/pharmacology
Analysis of Variance
Animals
Anti-Inflammatory Agents/*therapeutic use
Astrocyte
Astrocytes/*drug effects
Boyle Alexa M
Budge Kevin M
Case-Control Studies
CD44
Cells
Chemical
Cultured
Cytokines/genetics/metabolism
Databases
Female
Glial Fibrillary Acidic Protein/metabolism
GPNMB
Humans
Hyaluronan Receptors/*metabolism
Inflammation/*drug therapy/etiology
Journal of neuroinflammation
Male
Membrane Glycoproteins/*therapeutic use
Messenger/metabolism
Mice
Neal Matthew L
Neurotoxins/toxicity
Nitric Oxide/metabolism
Parkinson Disease/complications/*pathology
Reactive Oxygen Species/metabolism
Richardson Jason R
RNA
Safadi Fayez F
Signal Transduction/drug effects
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.neuro.2016.04.008" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.neuro.2016.04.008</a>
Pages
40–47
Volume
55
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
MPTP neurotoxicity is highly concordant between the sexes among BXD recombinant inbred mouse strains.
Publisher
An entity responsible for making the resource available
Neurotoxicology
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-07
Subject
The topic of the resource
*QTL; *Recombinant inbred mice; *Sex Characteristics; *Sex differences; 1-Methyl-4-phenyl-1; 2; 3; 4-Dihydroxyphenylacetic Acid/metabolism; 6-tetrahydropyridine/pharmacology; Animal; Animals; Corpus Striatum/drug effects/*metabolism; Disease Models; Dopamine/metabolism; Female; Gene Expression Regulation/drug effects/*genetics; Glial Fibrillary Acidic Protein/*metabolism; Homovanillic Acid/metabolism; Inbred Strains; Male; Mice; MPTP Poisoning/chemically induced/*pathology; Serotonin/metabolism; Species Specificity; Tyrosine 3-Monooxygenase/metabolism
Creator
An entity primarily responsible for making the resource
Alam Gelareh; Miller Diane B; O'Callaghan James P; Lu Lu; Williams Robert W; Jones Byron C
Description
An account of the resource
Continuing our previous work in which we showed wide-ranging strain differences in MPTP neurotoxicity in male mice among ten BXD recombinant inbred strains, we replicated our work in females from nine of the same strains. Mice received a single s.c. injection of 12.5mg/kg MPTP or saline. Forty-eight hours later the striatum was dissected for neurochemical analysis. Striatal dopamine (DA) and its metabolites, DOPAC and HVA, striatal serotonin (5-HT) and its metabolite, 5-HIAA, were analyzed using HPLC. Tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP), an astrocytic protein that increases during the astroglial response to neural injury, were measured using ELISA. There were wide genetic variations in the DA, DOPAC, HVA, TH and GFAP responses to MPTP. We also performed principal component analysis (PCA) on the difference values, saline minus MPTP, for DA, DOPAC, HVA and TH and mapped the dominant principal component to a suggestive QTL on chromosome 1 at the same location that we observed previously for males. Moreover, there were significant correlations between the sexes for the effect of MPTP on DA, HVA, and TH. Our findings suggest that the systems genetic approach as utilized here can help researchers understand the role of sex in individual differences. The same approach can pave the way to understand and pinpoint the genetic bases for individual differences in pathology attributable to toxicants. Such systems genetics approach has broad implications for elucidating gene-environment contributions to neurodegenerative diseases.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.neuro.2016.04.008" target="_blank" rel="noreferrer noopener">10.1016/j.neuro.2016.04.008</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*QTL
*Recombinant inbred mice
*Sex Characteristics
*Sex differences
1-Methyl-4-phenyl-1
2
2016
3
4-Dihydroxyphenylacetic Acid/metabolism
6-tetrahydropyridine/pharmacology
Alam Gelareh
Animal
Animals
Corpus Striatum/drug effects/*metabolism
Department of Family & Community Medicine
Disease Models
Dopamine/metabolism
Female
Gene Expression Regulation/drug effects/*genetics
Glial Fibrillary Acidic Protein/*metabolism
Homovanillic Acid/metabolism
Inbred Strains
Jones Byron C
Lu Lu
Male
Mice
Miller Diane B
MPTP Poisoning/chemically induced/*pathology
NEOMED College of Medicine
Neurotoxicology
O'Callaghan James P
Serotonin/metabolism
Species Specificity
Tyrosine 3-Monooxygenase/metabolism
Williams Robert W