Tamoxifen diminishes methamphetamine-induced striatal dopamine depletion in intact female and male mice.
Animals; Catecholamines/metabolism; Corpus Striatum/drug effects/*metabolism; Dopamine Uptake Inhibitors/*pharmacology; Dopamine/*metabolism; Estrogen Antagonists/*pharmacology; Female; Humans; Hypothalamus/metabolism; Inbred Strains; Male; Methamphetamine/*pharmacology; Mice; Neurotoxins/*pharmacology; Olfactory Bulb/metabolism; Organ Size/drug effects; Pituitary Gland/anatomy & histology; Tamoxifen/*pharmacology
It has been demonstrated that the nigrostriatal dopaminergic system of male mice is more sensitive to the neurotoxic effects of methamphetamine (MA). The basis for this difference can be related to oestrogen, which has the capacity to function as a neuroprotectant against neurotoxins that target the nigrostriatal dopaminergic system. We examined the effects of the anti-oestrogen, tamoxifen (TMX), upon MA-induced neurotoxicity of the nigrostriatal dopaminergic system in intact female and male CD-1 mice. Striatal dopamine concentrations of TMX-treated female and male mice receiving MA were significantly greater than mice receiving MA alone. In female, but not male, mice, oestrogen treatment also resulted in greater striatal dopamine concentrations compared to mice receiving MA alone. Interestingly, male mice treated with oestrogen were particularly sensitive to the acute toxic effects of MA and displayed no evidence of nigrostriatal neuroprotection. The dihydroxyphenylacetic acid/dopamine ratios following MA for female and male mice treated with TMX or females treated with oestrogen were significantly reduced compared to MA-treated mice and oestrogen + MA-treated male mice. No differences among the treatment groups were obtained for dopamine in the hypothalamus or olfactory bulb. These data demonstrate that TMX treatment of intact female and male mice diminishes striatal dopamine depletions to the nigrostriatal dopaminergic neurotoxin, MA. Oestrogen also displayed this capacity when administered to female, but accentuated acute toxicity in male mice. These effects are relatively specific for the nigrostriatal dopaminergic system. Such data suggest that TMX can function as a nigrostriatal dopaminergic neuroprotectant against MA-induced neurotoxicity in intact female and male mice.
Dluzen D E; McDermott J L; Anderson L I
Journal of neuroendocrinology
2001
2001-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1046/j.1365-2826.2001.00675.x" target="_blank" rel="noreferrer noopener">10.1046/j.1365-2826.2001.00675.x</a>
Developmental aspect of differences in hypothalamic preproneuropeptide y messenger ribonucleic Acid content in lean and genetically obese zucker rats.
The genetically obese Zucker rat is a well characterized model of early onset human obesity. Many of the endocrine and metabolic abnormalities of obese animals are common to other strains of genetically obese animals as well as morbidly obese humans. Neuropeptide Y (NPY), a potent orexigenic agent, was recently found to be elevated in adult obese animals compared to their lean littermates. In this study we first examined hypothalamic expression of preproNPY mRNA, using solution hybridization/ nuclease protection analysis, in phenotypically-matched, i.e. lean or obese, immature (5-week-old) and mature (33-week-old) animals. Although changes were not statistically different, a trend toward decreased hypothalamic preproNPY mRNA levels was detected in both lean and obese mature animals. We next compared hypothalamic preproNPY mRNA levels between age-matched lean and obese animals at 5, 14 and 33 weeks of age and found elevated preproNPY mRNA levels in obese rats at all three ages. These data suggest that increased levels of hypothalamic NPY are an early manifestation of the obese phenotype and may, therefore, contribute to hyperphagia and increased weight gain in obese Zucker rats.
Sanacora G; Finkelstein J A; Whitet J D
Journal of neuroendocrinology
1992
1992-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/j.1365-2826.1992.tb00179.x" target="_blank" rel="noreferrer noopener">10.1111/j.1365-2826.1992.tb00179.x</a>
Sex differences in K+-evoked striatal dopamine output from superfused striatal tissue fragments of reserpine-treated CD-1 mice.
Adrenergic Uptake Inhibitors/*metabolism; Animals; Corpus Striatum/anatomy & histology/*metabolism; Dopamine Agents/metabolism; Dopamine/*metabolism; Female; Male; Methamphetamine/metabolism; Mice; Potassium/*metabolism; Reserpine/*metabolism; Sex Factors; Tissue Culture Techniques; Vesicular Monoamine Transport Proteins/metabolism
Reserpine inhibits vesicular monoamine transporter-2 (VMAT-2) function and thereby impairs vesicular dopamine (DA) storage within nerve terminals. The present report compared the effects of reserpine treatment upon the striatal dopaminergic system in male and female mice as a means to assess potential sex differences in VMAT-2/DA storage function. After treatment with reserpine, male mice showed significantly greater striatal DA concentrations and K+ -evoked DA output from the striatum compared to females. By contrast, no statistically significant sex differences were observed in methamphetamine-evoked DA output in reserpine-treated mice. These results demonstrate a clear sex difference in the striatal dopaminergic responses to reserpine and suggest that females possess a more active VMAT-2/DA storage capacity, as indicated by the greater degree of deficits observed when VMAT-2/DA storage function is inhibited by reserpine. Such findings have important implications for understanding some of the bases for sex differences in neurotoxicity and neurodegeneration of the nigrostriatal dopaminergic system.
Ji J; McDermott J L; Dluzen D E
Journal of neuroendocrinology
2007
2007-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/j.1365-2826.2007.01581.x" target="_blank" rel="noreferrer noopener">10.1111/j.1365-2826.2007.01581.x</a>
Oestrogen Receptors and Signalling Pathways: Implications for Neuroprotective Effects of Sex Steroids in Parkinson's Disease
17 ss-oestradiol; Akt; beta messenger-rna; central-nervous-system; dopamine transporter; Endocrinology & Metabolism; er-alpha; GPER1; growth-factor receptor; GSK3 ss; induced dopamine depletion; ischemic brain-injury; monoamine transporter; MPTP; Neurosciences & Neurology; plasma-membrane; protein-coupled receptor; rat-brain; vesicular
Parkinsons disease (PD) is an age-related neurodegenerative disorder with a higher incidence in the male population. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, 17 beta-oestradiol but not androgens were shown to protect dopamine (DA) neurones. We report that oestrogen receptors (ER)a and beta distinctly contribute to neuroprotection against MPTP toxicity, as revealed by examining the membrane DA transporter (DAT), the vesicular monoamine transporter 2 (VMAT2) and tyrosine hyroxylase in ER wild-type (WT) and knockout (ERKO) C57Bl/6 male mice. Intact ERKO beta mice had lower levels of striatal DAT and VMAT2, whereas ERKOa mice were the most sensitive to MPTP toxicity compared to WT and ERKO beta mice and had the highest levels of plasma androgens. In both ERKO mice groups, treatment with 17 beta-oestradiol did not provide neuroprotection against MPTP, despite elevated plasma 17 beta-oestradiol levels. Next, the recently described membrane G protein-coupled oestrogen receptor (GPER1) was examined in female Macaca fascicularis monkeys and mice. GPER1 levels were increased in the caudate nucleus and the putamen of MPTP-monkeys and in the male mouse striatum lesioned with methamphetamine or MPTP. Moreover, neuroprotective mechanisms in response to oestrogens transmit via Akt/glycogen synthase kinase-3 (GSK3) signalling. The intact and lesioned striata of 17 beta-oestradiol treated monkeys, similar to that of mice, had increased levels of pAkt (Ser 473)/beta III-tubulin, pGSK3 (Ser 9)/beta III-tubulin and Akt/beta III-tubulin. Hence, ERa, ER beta and GPER1 activation by oestrogens is imperative in the modulation of ER signalling and serves as a basis for evaluating nigrostriatal neuroprotection.
Al Sweidi S; Sanchez M G; Bourque M; Morissette M; Dluzen D; Di Paolo T
Journal of Neuroendocrinology
2012
2012-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1111/j.1365-2826.2011.02193.x" target="_blank" rel="noreferrer noopener">10.1111/j.1365-2826.2011.02193.x</a>
Interactive effects of tamoxifen and oestrogen upon the nigrostriatal dopaminergic system: Long-term treatments
receptors; Neurosciences & Neurology; Endocrinology & Metabolism; estrogen; binding; catecholamines; brain; striatum; time; amphetamine; estradiol; antiestrogens; ovarian steroids; sexual-behavior; anti-oestrogens
In the present report adult female rats were ovariectomized (OVX) and assigned to one of four treatment conditions. Treatments consisted of administering pellets containing 17 beta-oestradiol (E), tamoxifen (TMX), a combination of TMX and E or no further treatment (OVX), Animals received these treatments immediately following OVX and were maintained in these conditions for a 40-day period. Subsequently, the corpus striatum (CS) was dissected from each animal and prepared for determinations of basal and amphetamine stimulated DA output using in-vitro superfusion. No statistically significant differences among the four treatment groups were obtained for basal dopamine output. The highest levels of amphetamine-stimulated dopamine responses were obtained from E treated rats. These values were significantly greater than that obtained from OVX rats and rats treated with a combination of TMX + E. The significance of these findings is that they indicate both a non-traditional central nervous system site and mechanism of action through which tamoxifen-oestrogen interactions can function. Such data may have important implications for administration of tamoxifen to premenopausal women as this anti-oestrogen may compromise nigrostriatal dopaminergic function under conditions where oestrogenic modulation is present.
McDermott J L; Anderson L I; Dluzen D E
Journal of Neuroendocrinology
1999
1999-10
Journal Article or Conference Abstract Publication
n/a