Neural Steroidogenic Enzymes and Brain Function

University Of California Los Angeles, Los Angeles CA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): 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.