Steroid hormones are powerful signaling molecules in the CNS and there is substantial evidence that steroid synthesis is a property of the brain. Steroids synthesized in brain (neurosteroids) have many reported functions, but there is still doubt about the full biological importance of neurosteroidogenesis. Studies of songbirds are identifying important functions of brain steroid synthesis. We have excellent evidence that steroids synthesized in the songbird brain play a key role in the development of song control circuits and in the activation of some adult behaviors. Recently, we created songbird specific probes and found that developmentally, steroidogenic enzymes are concentrated near the walls of the ventricles where neurogenesis is known to occur. We hypothesize that ventricular steroidogenesis in songbirds impacts the proper birth, differentiation or migration of neurons destined to enter brain regions required for masculine song expression. A related mechanism may persist in adults that retain prominent neural plasticity. After neural injury, we find the estrogen synthetic enzyme aromatase is strongly expressed in radial glia with aromatase-positive fibers guiding newly generated cells. We hypothesize that additional steroidogenic enzymes must be expressed in or near these radial glia to provide substrates for estrogen synthesis to assist in neural repair. Lastly, we predict that these enzymes are up-regulated during non-breeding seasons in some species to activate steroid-dependent aggressive behaviors. In studies proposed here, we will test these hypotheses in slice-culture preparations of developing zebra finch brain, after neural injury to adult zebra finches and in a seasonal breeding songbird. We will inhibit steroidogenic enzymes and examine the effects on steroid synthesis, cytogenesis and differentiation, masculine brain development and behavior. These studies will reveal important actions of neurosteroids in neural growth, plasticity and repair that will have important implications in basic developmental neurobiology and in treatments of neurodegenerative disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH061994-06
Application #
6894008
Study Section
Special Emphasis Panel (ZRG1-NNB (01))
Program Officer
Winsky, Lois M
Project Start
2000-08-01
Project End
2009-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
6
Fiscal Year
2005
Total Cost
$277,137
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Rensel, Michelle A; Schlinger, Barney A (2016) Determinants and significance of corticosterone regulation in the songbird brain. Gen Comp Endocrinol 227:136-42
Rensel, Michelle A; Ellis, Jesse M S; Harvey, Brigit et al. (2015) Sex, estradiol, and spatial memory in a food-caching corvid. Horm Behav 75:45-54
Schlinger, Barney A (2015) Steroids in the Avian Brain: Heterogeneity across Space and Time. J Ornithol 156:419-424
Schlinger, Barney A; Remage-Healey, Luke; Rensel, Michelle (2014) Establishing regional specificity of neuroestrogen action. Gen Comp Endocrinol 205:235-41
Rensel, M A; Salwiczek, L; Roth, J et al. (2013) Context-specific effects of estradiol on spatial learning and memory in the zebra finch. Neurobiol Learn Mem 100:41-7
Remage-Healey, Luke; Saldanha, Colin J; Schlinger, Barney A (2011) Estradiol synthesis and action at the synapse: evidence for ""synaptocrine"" signaling. Front Endocrinol (Lausanne) 2:28
Katz, Amnon; Oyama, Randy K; Feng, Ni et al. (2010) 11beta-hydroxysteroid dehydrogenase type 2 in zebra finch brain and peripheral tissues. Gen Comp Endocrinol 166:600-5
Remage-Healey, Luke; London, Sarah E; Schlinger, Barney A (2010) Birdsong and the neural production of steroids. J Chem Neuroanat 39:72-81

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