During early brain development, steroid hormone exposure differentiates male from female brain. Although there are numerous physiological and behavioral differences between men and women, perhaps the most profound sex differences are in neurological and psychiatric disorders. For example, women are more likely to exhibit signs of depression, multiple sclerosis, and Alzheimer's disease. Men are more likely to exhibit signs of attention-deficit hyperactivity, autism, and dyslexia. As most sex differences in the brain are a result of early steroid hormone exposure, it is possible that sex differences in some disorders are partly influenced by abnormal steroid receptor action in developing brain. Therefore it is important to understand how steroid receptor activity is regulated in developing brain. Previously, it was assumed that steroid receptors were only activated by steroid hormones; however, recent data indicate that steroid receptors are also activated in the absence of steroid, referred to as ligand-independent activation. Although numerous investigators are currently studying ligand-independent activation of steroid receptors in cell culture assays and in adult female brain, few studies investigate the role of ligand-independent activation of steroid receptors in brain development. We plan to investigate the functional role ligand-independent activation of estrogen receptors (ER) in developing brain. Our recent data indicate that acute changes in dopamine transmission during the first few days of life can dramatically alter the developmental organization of social play behavior by activating ER in a ligand-independent manner. We believe that these data are not only exciting in that they suggest a potential steroid hormone independent mechanism for sexual differentiation of the brain, but they also investigate the developmental organization of social play behavior. As social play behavior is dramatically disrupted in children with Autism and Asperger's syndrome, and social play behavior in rodents has been used as a rodent model for the study of autism, it is possible that these data will further our understanding of how sexually dimorphic social disorders occur during brain development. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH072956-01A2
Application #
7100313
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Sieber, Beth-Anne
Project Start
2006-08-01
Project End
2011-05-31
Budget Start
2006-08-01
Budget End
2007-05-31
Support Year
1
Fiscal Year
2006
Total Cost
$310,475
Indirect Cost
Name
University of Wisconsin Madison
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Edelmann, Michelle N; Demers, Catherine H; Auger, Anthony P (2013) Maternal touch moderates sex differences in juvenile social play behavior. PLoS One 8:e57396
Forbes-Lorman, Robin M; Rautio, Jared J; Kurian, Joseph R et al. (2012) Neonatal MeCP2 is important for the organization of sex differences in vasopressin expression. Epigenetics 7:230-8
Kolodkin, M H; Auger, A P (2011) Sex difference in the expression of DNA methyltransferase 3a in the rat amygdala during development. J Neuroendocrinol 23:577-83
Auger, Anthony P; Jessen, Heather M; Edelmann, Michelle N (2011) Epigenetic organization of brain sex differences and juvenile social play behavior. Horm Behav 59:358-63
Edelmann, Michelle N; Auger, Anthony P (2011) Epigenetic impact of simulated maternal grooming on estrogen receptor alpha within the developing amygdala. Brain Behav Immun 25:1299-304
Auger, Catherine J; Coss, Dylan; Auger, Anthony P et al. (2011) Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain. Proc Natl Acad Sci U S A 108:4242-7
Fuxjager, Matthew J; Forbes-Lorman, Robin M; Coss, Dylan J et al. (2010) Winning territorial disputes selectively enhances androgen sensitivity in neural pathways related to motivation and social aggression. Proc Natl Acad Sci U S A 107:12393-8
Jessen, Heather M; Kolodkin, Mira H; Bychowski, Meaghan E et al. (2010) The nuclear receptor corepressor has organizational effects within the developing amygdala on juvenile social play and anxiety-like behavior. Endocrinology 151:1212-20
Schuler, Linda A; Auger, Anthony P (2010) Psychosocially influenced cancer: diverse early-life stress experiences and links to breast cancer. Cancer Prev Res (Phila) 3:1365-70
Kurian, Joseph R; Olesen, Kristin M; Auger, Anthony P (2010) Sex differences in epigenetic regulation of the estrogen receptor-alpha promoter within the developing preoptic area. Endocrinology 151:2297-305

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