Estrogens are involved in a variety of physiological processes, including regulation of arousal. Our studies indicate that estrogens increase three separate components of arousal;running wheel and home cage motor activity, sensory responsiveness (predominantly to tactile stimulation) and emotionality (fear conditioning) are all increased in estradiol-treated animals as compared to oil-treated animals. Microarray studies revealed that lipocalin-type prostaglandin D synthase (L-PGDS) is specifically altered in select brain regions of estrogen-treated mice. L-PDGS catalyses the formation of prostaglandin D2 (PGD2). PGD2 is an endogenous somnogen that induces c-FOS expression on sleep-active neurons in the ventrolateral preoptic area (VLPO). The sleep-promoting effects of PGD2 are mediated by increased A2A receptor binding in VLPO neurons. A2A agonists can directly excite a subpopulation of VLPO neurons. Taken together, we hypothesize that PGD2 and adenosine are key molecules involved in the signaling cascade by which estrogens increase arousal. Specifically, we will test whether the arousal-promoting effects of estrogen are mediated via a suppression of A2A signaling in the VLPO. The proposed experiments will provide critical insight into the signaling cascade underlying estrogen- mediated increases in arousal, and possibly reveal new therapeutic avenues in the treatment of disorders of vigilance and arousal.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL086018-03
Application #
7586783
Study Section
Special Emphasis Panel (ZRG1-F02A-A (20))
Program Officer
Rothgeb, Ann E
Project Start
2007-04-01
Project End
2009-08-31
Budget Start
2009-04-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2009
Total Cost
$22,020
Indirect Cost
Name
Rockefeller University
Department
Biology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Ribeiro, Ana C; Ågmo, Anders; Musatov, Sergei et al. (2016) Silencing Estrogen Receptor-? with siRNA in the Intact Rodent Brain. Methods Mol Biol 1366:343-352
Ribeiro, Ana C; Musatov, Sergei; Shteyler, Anna et al. (2012) siRNA silencing of estrogen receptor-ýý expression specifically in medial preoptic area neurons abolishes maternal care in female mice. Proc Natl Acad Sci U S A 109:16324-9
Ribeiro, Ana C; Ceccarini, Giovanni; Dupre, Christophe et al. (2011) Contrasting effects of leptin on food anticipatory and total locomotor activity. PLoS One 6:e23364
Ribeiro, Ana C; Pfaff, Donald W; Devidze, Nino (2009) Estradiol modulates behavioral arousal and induces changes in gene expression profiles in brain regions involved in the control of vigilance. Eur J Neurosci 29:795-801
Ribeiro, Ana C; LeSauter, Joseph; Dupre, Christophe et al. (2009) Relationship of arousal to circadian anticipatory behavior: ventromedial hypothalamus: one node in a hunger-arousal network. Eur J Neurosci 30:1730-8