1
40
1
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Text
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<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
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Title
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MPTP neurotoxicity is highly concordant between the sexes among BXD recombinant inbred mouse strains.
Publisher
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Neurotoxicology
Date
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2016
2016-07
Subject
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*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
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Alam Gelareh; Miller Diane B; O'Callaghan James P; Lu Lu; Williams Robert W; Jones Byron C
Description
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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.
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<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>
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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