QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 11, 2006, 26(2):535-541; doi:10.1523/JNEUROSCI.3008-05.2006

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Xu, K. Articles by Schwarzschild, M. A. Search for Related Content PubMed PubMed Citation Articles by Xu, K. Articles by Schwarzschild, M. A.

 Previous Article  |  Next Article 

Neurobiology of Disease
Estrogen Prevents Neuroprotection by Caffeine in the Mouse 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Model of Parkinson's Disease

Kui Xu,¹ Yuehang Xu,¹ Deborah Brown-Jermyn,¹ Jiang-Fan Chen,² Alberto Ascherio,³ Dean E. Dluzen,⁴ and Michael A. Schwarzschild¹

¹Molecular Neurobiology Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, ²Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, ³Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, and ⁴Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272

Epidemiological studies have strongly linked caffeine consumption with a reduced risk of developing Parkinson's disease (PD) in men. Interestingly, in women, this inverse association is present only in those who have not taken postmenopausal estrogens, suggesting an interaction between the influences of estrogen and caffeine use on the risk of PD. To explore a possible biological basis for this interaction, we systematically investigated how the neuroprotective effect of caffeine is influenced by gender, ovariectomy (OVX), and then exogenous estrogen in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. (1) Caffeine treatment produced a dose-dependent attenuation of MPTP-induced striatal dopamine loss in both young and retired breeder (RB) male, but not female, mice. (2) In female mice (both young and RB), caffeine was less potent or altogether ineffective as a neuroprotectant after sham surgery compared to OVX or after OVX plus estrogen replacement compared to OVX plus placebo treatment. (3) Estrogen treatment also prevented the protection of caffeine against dopamine loss in young male mice. (4) Consistent with the putative protective effect of estrogen, female and OVX plus estrogen mice were relatively resistant to MPTP toxicity compared to male and OVX plus placebo mice, respectively. (5) There was no overall difference in brain levels of caffeine and its metabolites between OVX plus placebo and OVX plus estrogen mice. Together, these results suggest that estrogen can occlude and thereby prevent the neuroprotective effect of caffeine in a model of PD neurodegeneration, supporting a biological basis for the interaction between estrogen and caffeine in modifying the risk of PD.

Key words: adenosine A_2A receptor; dopamine; gender; methylxanthine; ovariectomy; striatum

---

Received July 20, 2005; revised October 20, 2005; accepted November 21, 2005.

This article has been cited by other articles:

				S. Guerreiro, D. Toulorge, E. Hirsch, M. Marien, P. Sokoloff, and P. P. Michel Paraxanthine, the Primary Metabolite of Caffeine, Provides Protection against Dopaminergic Cell Death via Stimulation of Ryanodine Receptor Channels Mol. Pharmacol., October 1, 2008; 74(4): 980 - 989. [Abstract] [Full Text] [PDF]

				F. S. Jones, J. Jing, A. H. Stonehouse, A. Stevens, and G. M. Edelman Caffeine Stimulates Cytochrome Oxidase Expression and Activity in the Striatum in a Sexually Dimorphic Manner Mol. Pharmacol., September 1, 2008; 74(3): 673 - 684. [Abstract] [Full Text] [PDF]

				X. Gao, H. Chen, M. A. Schwarzschild, D. B. Glasser, G. Logroscino, E. B. Rimm, and A. Ascherio Erectile Function and Risk of Parkinson's Disease Am. J. Epidemiol., December 15, 2007; 166(12): 1446 - 1450. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help