Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure

Yu Luo, Yun Wang, Serena Y. Kuang, Yung Hsiao Chiang, Barry Hoffer

研究成果: 雜誌貢獻文章

18 引文 (Scopus)

摘要

The abuse of psychostimulants, such as methamphetamine (METH), is prevalent in young adults and could lead to longterm adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to nai{dotless}̈ve mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH) immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr) as well as decreased dopamine transporter (DAT) level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals.

原文英語
文章編號e15193
期刊PLoS One
5
發行號12
DOIs
出版狀態已發佈 - 2010

指紋

Methamphetamine
adolescence
young adults
Toxicity
Young Adult
toxicity
mice
dopamine
tyrosine 3-monooxygenase
neurons
adverse effects
Dopaminergic Neurons
transporters
Neurons
genes
Genes
mutation
brain
Dopamine Plasma Membrane Transport Proteins
Tyrosine 3-Monooxygenase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

引用此文

Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure. / Luo, Yu; Wang, Yun; Kuang, Serena Y.; Chiang, Yung Hsiao; Hoffer, Barry.

於: PLoS One, 卷 5, 編號 12, e15193, 2010.

研究成果: 雜誌貢獻文章

@article{783a064729bf4df9a653d596d1916e30,
title = "Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure",
abstract = "The abuse of psychostimulants, such as methamphetamine (METH), is prevalent in young adults and could lead to longterm adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to nai{dotless}̈ve mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH) immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr) as well as decreased dopamine transporter (DAT) level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals.",
author = "Yu Luo and Yun Wang and Kuang, {Serena Y.} and Chiang, {Yung Hsiao} and Barry Hoffer",
year = "2010",
doi = "10.1371/journal.pone.0015193",
language = "English",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure

AU - Luo, Yu

AU - Wang, Yun

AU - Kuang, Serena Y.

AU - Chiang, Yung Hsiao

AU - Hoffer, Barry

PY - 2010

Y1 - 2010

N2 - The abuse of psychostimulants, such as methamphetamine (METH), is prevalent in young adults and could lead to longterm adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to nai{dotless}̈ve mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH) immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr) as well as decreased dopamine transporter (DAT) level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals.

AB - The abuse of psychostimulants, such as methamphetamine (METH), is prevalent in young adults and could lead to longterm adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to nai{dotless}̈ve mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH) immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr) as well as decreased dopamine transporter (DAT) level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals.

UR - http://www.scopus.com/inward/record.url?scp=78649939502&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649939502&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0015193

DO - 10.1371/journal.pone.0015193

M3 - Article

C2 - 21151937

AN - SCOPUS:78649939502

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e15193

ER -