Accession Number:

ADA460739

Title:

Caffeine, Adenosine Receptors and Estrogen in Toxin Models of Parkinson's Disease

Descriptive Note:

Annual rept. 1 Oct 2004-30 Sep 2005

Corporate Author:

MASSACHUSETTS GENERAL HOSPITAL BOSTON

Personal Author(s):

• Schwarzschild, Michael A.

Report Date:

2005-10-01

Pagination or Media Count:

74.0

Abstract:

Substantial progress has been made toward each of the 3 Specific Aims SAs of our research project, Caffeine, adenosine receptors andestrogen in toxin models of Parkinsons disease PD. The overarching hypothesis of the project is that multiple environmental protectants and toxins interact to influence of the health of the dopaminergic neurons lost in PD. To that end we are characterizing the interplay between several environmental agents pesticides, caffeine and estrogen that are leading candidate modulators of PD risk. A major finding and publication of this project SA 3 in its first year entails our demonstration that estrogen can prevent the neuroprotective effect of caffeine in the mouse MPTP model of PD. We have obtained evidence that endogenous estrogen in females andexogenous estrogen in males and in ovariectomized females can prevent the protective effect of caffeine on MPTP- induced loss of brain dopamine. Estrogen did not alter caffeine pharmacokinetics arguing for a downstream estrogen-caffeine interaction in the modification of dopaminergic neuron injury. These findings establish an animal model of estrogen-caffeine interactions in the modification of PD risk in humans, along with the opportunity to understand its molecular mechanisms. In addition, our laboratory and human data for this interaction are now sufficiently compelling to influence the design and interpretation of neuroprotection trials of estrogen or caffeine currently underway or under consideration. Ultimately, a better understanding of the interplay between environmental factors like caffeine estrogen may suggest effective preventative as well as therapeutic strategies for this neurodegenerative disorder.

Descriptors:

• *CAFFEINE
• *ADENOSINE
• *ESTROGENS
• *PARKINSONS DISEASE
• RISK
• STRATEGY
• DAMAGE
• BRAIN
• ORDER DISORDER TRANSFORMATIONS
• PROTECTION
• THERAPY
• NERVE CELLS
• MOTOR NEURONS
• LOSSES
• PHARMACOKINETICS
• MOLECULAR PROPERTIES
• DOPAMINE
• TOXINS AND ANTITOXINS
• RECEPTOR SITES(PHYSIOLOGY)
• PESTICIDES

Subject Categories:

• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE