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The impact of gender and estrogen on striatal dopaminergic neurotoxicity.
Ann N Y Acad Sci. 1998 May 30; 844:153-65.AN

Abstract

The reproductive properties of estrogen are well established, but it is now evident that this steroid hormone has substantial modulatory capabilities in nonreproductive systems. For example, estrogen may be neuroprotective as Alzheimer's disease progresses more slowly in women receiving hormone replacement therapy, and Parkinson's disease affects more men than women. Gender affects both the functional biochemical responses of the nigral-striatal pathway to dopaminergically active compounds. To begin to evaluate the possible neuroprotective effects of estrogen in this pathway, we first determined if gender affected dopaminergic striatal neurotoxicity induced by two different neurotoxicants, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Both agents induced greater neurotoxicity in males than females as evidenced by greater striatal dopamine (DA) depletions. An examination of striatal levels of 1-methyl-4-phenylpyridium ion (MPP+) following MPTP treatment established that the observed gender differences were not due to metabolic/pharmacokinetic variables. The neurotoxicity of MPTP was then examined in ovariectomized (OVX) mice. Estrogen replacement reduced the DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletions as well as the glial fibrillary acidic protein (GFAP) elevation induced by MPTP, which indicates that estrogen has neuroprotective properties in this model of striatal dopaminergic neurotoxicity. Surprisingly, estrogen supplementation did not protect against the neurotoxic effects of MPTP in intact 2-yr-old intact female mice, suggesting that low endogenous levels of estrogen may provide neuroprotection.

Authors+Show Affiliations

Toxiology & Molecular Biology Branch, CDC/NIOSH, Morgantown, West Virginia 26505-2888, USA. dum6@niords1.em.cdc.govNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9668673

Citation

Miller, D B., et al. "The Impact of Gender and Estrogen On Striatal Dopaminergic Neurotoxicity." Annals of the New York Academy of Sciences, vol. 844, 1998, pp. 153-65.
Miller DB, Ali SF, O'Callaghan JP, et al. The impact of gender and estrogen on striatal dopaminergic neurotoxicity. Ann N Y Acad Sci. 1998;844:153-65.
Miller, D. B., Ali, S. F., O'Callaghan, J. P., & Laws, S. C. (1998). The impact of gender and estrogen on striatal dopaminergic neurotoxicity. Annals of the New York Academy of Sciences, 844, 153-65.
Miller DB, et al. The Impact of Gender and Estrogen On Striatal Dopaminergic Neurotoxicity. Ann N Y Acad Sci. 1998 May 30;844:153-65. PubMed PMID: 9668673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The impact of gender and estrogen on striatal dopaminergic neurotoxicity. AU - Miller,D B, AU - Ali,S F, AU - O'Callaghan,J P, AU - Laws,S C, PY - 1998/7/21/pubmed PY - 1998/7/21/medline PY - 1998/7/21/entrez SP - 153 EP - 65 JF - Annals of the New York Academy of Sciences JO - Ann N Y Acad Sci VL - 844 N2 - The reproductive properties of estrogen are well established, but it is now evident that this steroid hormone has substantial modulatory capabilities in nonreproductive systems. For example, estrogen may be neuroprotective as Alzheimer's disease progresses more slowly in women receiving hormone replacement therapy, and Parkinson's disease affects more men than women. Gender affects both the functional biochemical responses of the nigral-striatal pathway to dopaminergically active compounds. To begin to evaluate the possible neuroprotective effects of estrogen in this pathway, we first determined if gender affected dopaminergic striatal neurotoxicity induced by two different neurotoxicants, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Both agents induced greater neurotoxicity in males than females as evidenced by greater striatal dopamine (DA) depletions. An examination of striatal levels of 1-methyl-4-phenylpyridium ion (MPP+) following MPTP treatment established that the observed gender differences were not due to metabolic/pharmacokinetic variables. The neurotoxicity of MPTP was then examined in ovariectomized (OVX) mice. Estrogen replacement reduced the DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletions as well as the glial fibrillary acidic protein (GFAP) elevation induced by MPTP, which indicates that estrogen has neuroprotective properties in this model of striatal dopaminergic neurotoxicity. Surprisingly, estrogen supplementation did not protect against the neurotoxic effects of MPTP in intact 2-yr-old intact female mice, suggesting that low endogenous levels of estrogen may provide neuroprotection. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/9668673/The_impact_of_gender_and_estrogen_on_striatal_dopaminergic_neurotoxicity_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=1998&volume=844&spage=153 DB - PRIME DP - Unbound Medicine ER -