Men and women suffer disproportionally from specific neurological and psychiatric disorders and the basis for this difference remains unclear. However, given that males and females are exposed to different levels of steroids throughout development, a role for these hormones in the etiology of sexually dimorphic neurological disorders is strongly suggested. Investigating the consequences of this dimorphic exposure will help elucidate the mechanisms of steroid action on the developing brain. Previous research in our laboratory implicates astrocytes as an important target of steroid hormone action in select regions of the developing perinatal rodent brain. The preoptic area (POA) is a major brain region controlling sex-typic behavior and physiology, and preliminary data suggest that astrocytes of this region are also responsive to steroids. We have found that as early as the day of birth, the morphology of astrocytes of the POA are sexually dimorphic. The importance of astrocytes in the establishment of neuronal architecture is becoming increasingly evident. The goal of this proposal is to elucidate the mechanism(s) of steroid-mediated changes in POA neuronal morphology involving neighboring steroid-sensitive astrocytes. Hormonal manipulation experiments will establish the steroid specificity determining neuron differentiation within the developing POA. To begin to determine the functional relationship between the two cell types, experiments will identify the components of an astrocyte-to-neuron communication cascade and examine the effect of steroid manipulation on this system. Pharmacological manipulations and the use of antisense oligodeoxynucleotides will explore the roles of prostaglandin E2 and the activation of their cognate receptors in this signal transduction mechanism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30MH012862-04
Application #
6741886
Study Section
Special Emphasis Panel (ZRG1-MDCN-6 (01))
Program Officer
Curvey, Mary F
Project Start
2002-04-16
Project End
2007-04-15
Budget Start
2004-04-16
Budget End
2005-04-15
Support Year
4
Fiscal Year
2004
Total Cost
$34,821
Indirect Cost
Name
University of Maryland Baltimore
Department
Physiology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201