Gender Differences in Methamphetamine-Induced mRNA Associated with Neurodegeneration in the Mouse Nigrostriatal Dopaminergic System

Dluzen, Dean E.; Tweed, Christopher W.; Anderson, Linda I.; Laping, Nicholas J.

doi:10.1159/000070278

Cited by 42 publications

(32 citation statements)

References 34 publications

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“…In MPTP models of PD, female mice have been reported to be more resistant to the dopaminedepleting effects of the toxin (Disshon and Dluzen, 2000;Dluzen, 1996;Dluzen et al, 1996;Dluzen et al, 2003;Freyaldenhoven et al, 1996;Miller et al, 1998;Nishino et al, 1998;Tamas et al, 2005). Similarly, male rats show greater susceptibility to toxicity of 6-OHDA when measured either by depletion of dopaminergic neurons or by behavioral recovery (Cass et al, 2005;Datla et al, 2003;Gillies et al, 2004;Murray et al, 2003;Tamas et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Effects of gender on nigral gene expression and parkinson disease

Cantuti-Castelvetri

Keller-McGandy

Bouzou

et al. 2007

Neurobiology of Disease

214

212

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To identify gene expression patterns in human dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of male and female control and Parkinson disease (PD) patients, we harvested DA neurons from frozen SNc from 16 subjects (4 male PD, 4 female PD, 4 male and 4 female controls) using Laser Capture microcrodissection and microarrays. We assessed for enrichment of functional categories with a hypergeometric distribution. The data were validated with QPCR.We observed that gender has a pervasive effect on gene expression in DA neurons. Genes upregulated in females relative to males are mainly involved in signal transduction and neuronal maturation, while in males some of the upregulated genes (alpha-synuclein and PINK1) were previously implicated in the pathogenesis of PD. In females with PD we found alterations in genes with protein kinase activity, genes involved in proteolysis and WNT signaling pathway, while in males with PD there were alterations in protein-binding proteins and copper-binding proteins.Our data reveal broad gender-based differences in gene expression in human dopaminergic neurons of SNc that may underlie the predisposition of males to PD. Moreover, we show that gender influences the response to PD, suggesting that the nature of the disease and the response to treatment may be gender-dependent.

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Section: Discussionmentioning

confidence: 99%

Effects of gender on nigral gene expression and parkinson disease

Cantuti-Castelvetri

Keller-McGandy

Bouzou

et al. 2007

Neurobiology of Disease

214

212

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“…As glial response is associated with hypermetabolism (Roh et al, 1998), the absence of frontal hypometabolism in female MA users in the current study may be associated with enhanced glial repair response to MA in females rather than males. After MA exposure, female mice have been reported to express augmented mRNA of glial fibrillary acidic protein, which is associated with glial repair response to brain injury (Dluzen et al, 2003;Garcia-Segura et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Frontal Glucose Hypometabolism in Abstinent Methamphetamine Users

Kim

Lyoo

Hwang

et al. 2005

Neuropsychopharmacol

110

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Changes in relative regional cerebral glucose metabolism (rCMRglc) and their potential gender differences in abstinent methamphetamine (MA) users were explored. Relative rCMRglc, as measured by 18 F-fluorodeoxyglucose positron emission tomography, and frontal executive functions, as assessed by Wisconsin card sorting test (WCST), were compared between 35 abstinent MA users and 21 healthy comparison subjects. In addition, male and female MA users and their gender-matched comparison subjects were compared to investigate potential gender differences. MA users had lower rCMRglc levels in the right superior frontal white matter and more perseveration and nonperseveration errors in the WCST, relative to healthy comparison subjects. Relative rCMRglc in the frontal white matter correlated with number of errors in the WCST in MA users. In the subanalysis for gender differences, lower rCMRglc in the frontal white matter and more errors in the WCST were found only in male MA users, not in female MA users, relative to their gender-matched comparison subjects. The current findings suggest that MA use causes persistent hypometabolism in the frontal white matter and impairment in frontal executive function. Our findings also suggest that the neurotoxic effect of MA on frontal lobes of the brain might be more prominent in men than in women.

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“…One important implication related to this issue is that of NSDA neurodegeneration and neurotoxicity. When treated with equivalent doses of neurotoxins which target the NSDA system, the degree of neurodegeneration observed in males is significantly greater than that in female as obtained in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [7,8,9], 6-hydroxydopamine [10, 11] and the psychostimulant methamphetamine (MA) [12,13,14,15,16,17,18,19]. …”

Section: Introductionmentioning

confidence: 99%

“…First, notable gender differences in use and characteristics of response to MA have been reported [20]. Second, since high doses and/or repeated treatment can produce neurodegeneration of the NSDA system, the significantly greater amount of striatal dopamine (DA) depletion in response to MA treatment within male mice [12,13,14,15,16,17,18,19] may serve to model NSDA neurodegenerative conditions like Parkinson’s disease, which also generally shows a higher incidence in males [21,22,23,24,25]. Third, the degree of toxicity to MA differs between male and female mice, as mortality rates to MA are greater in males [26].…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in Methamphetamine-Evoked Striatal Dopamine Output Are Abolished following Gonadectomy: Comparisons with Potassium-Evoked Output and Responses in Prepubertal Mice

Dluzen

Salvaterra²

2005

Neuroendocrinology

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Sex differences are reported for methamphetamine (MA)-induced neurotoxicity of the nigrostriatal dopaminergic system. In an attempt to understand some of the bases for these differences, we investigated MA-evoked dopamine (DA) responses from superfused striatal tissue fragments of intact and male and female CD-1 mice. These responses were compared with that of gonadectomized mice, potassium-evoked DA responses in intact mice and responses in prepubertal mice. In experiment 1, DA responses were tested using infusion of MA at doses of 1, 10, 100 and 1,000 µM. In intact mice, mean peak MA-evoked DA responses were consistently increased and significantly greater in male vs. female mice at the 1,000 µM dose. No such significant differences were observed between gonadectomized male vs. female mice (experiment 2). In contrast to MA, potassium-stimulated DA responses were increased in intact female mice, with statistically significant differences at doses of 30 and 60 mM (experiment 3). No statistically significant differences between intact prepubertal male and female mice were obtained in response to a 1,000 µM dose of MA (experiment 4) or to a 60 mM dose of potassium (experiment 5). These results indicate that intact male mice show greater sensitivity to MA-evoked DA output. This sex difference is abolished following gonadectomy, is not observed with potassium, nor is it present in prepubertal mice. The increased sensitivity to MA shown by intact males may be related to the greater degree of striatal dopaminergic neurotoxicity observed in male mice in response to this psychostimulant and appears to be attributable to differences in gonadal steroid hormones between male and female mice.

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Gender Differences in Methamphetamine-Induced mRNA Associated with Neurodegeneration in the Mouse Nigrostriatal Dopaminergic System

Cited by 42 publications

References 34 publications

Effects of gender on nigral gene expression and parkinson disease

Effects of gender on nigral gene expression and parkinson disease

Frontal Glucose Hypometabolism in Abstinent Methamphetamine Users

Sex Differences in Methamphetamine-Evoked Striatal Dopamine Output Are Abolished following Gonadectomy: Comparisons with Potassium-Evoked Output and Responses in Prepubertal Mice

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