The proposal has the long term goal of determining the factors that cause sex differences in structure, function, and susceptibility to disease in mesencephalic dopamine systems. The studies will investigate the cellular and molecular mechanisms by which sex chromosome genes induce sex differences in phenotype of dopaminergic neurons in vivo and in vitro. Studies will determine whether the sex chromosome effect is due to genes on the X or Y chromosomes; whether steroid hormones of the Sry gene participate in the induction of sex differences; when during development the sex chromosome effect occurs; whether the sex chromosome effect is direct or indirect on dopamine neurons; the cellular mechanisms of the sex chromosome effect; and whether the sex chromosomes contribute to sex differences in the development and adult structure of the nigrostriatal dopamine system in vivo. The proposed studies will contribute to an understanding of the principles of sexual differentiation of the brain. At issue are the molecular mechanisms by which male and female brains differ, which is relevant to the biological basis of abnormalities of sexual differentiation, and to the explanation of sex differences in neurological and psychiatric disease, not only of those that affect dopamine systems (e.g., Parkinson's Disease, Tardive Dyskinesia, Tourette's Syndrome, schizophrenia), but other sexually dimorphic diseases as well. (e.g., Multiple Sclerosis). Understanding sex differences in brain function will help develop sex-specific strategies for treatment of brain diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS045966-01
Application #
6601786
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Mitler, Merrill
Project Start
2003-09-30
Project End
2007-06-30
Budget Start
2003-09-30
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$325,969
Indirect Cost
Name
University of California Los Angeles
Department
Social Sciences
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Burgoyne, Paul S; Arnold, Arthur P (2016) A primer on the use of mouse models for identifying direct sex chromosome effects that cause sex differences in non-gonadal tissues. Biol Sex Differ 7:68
Arnold, Arthur P (2009) The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues. Horm Behav 55:570-8
Arnold, Arthur P (2009) Mouse models for evaluating sex chromosome effects that cause sex differences in non-gonadal tissues. J Neuroendocrinol 21:377-86
Arnold, Arthur P; Chen, Xuqi (2009) What does the ""four core genotypes"" mouse model tell us about sex differences in the brain and other tissues? Front Neuroendocrinol 30:1-9
Chen, Xuqi; Grisham, William; Arnold, Arthur P (2009) X chromosome number causes sex differences in gene expression in adult mouse striatum. Eur J Neurosci 29:768-76
van Nas, Atila; Guhathakurta, Debraj; Wang, Susanna S et al. (2009) Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks. Endocrinology 150:1235-49
Arnold, Arthur P; van Nas, Atila; Lusis, Aldons J (2009) Systems biology asks new questions about sex differences. Trends Endocrinol Metab 20:471-6
Gioiosa, Laura; Chen, Xuqi; Watkins, Rebecca et al. (2008) Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine in mice. Horm Behav 53:124-30
Gioiosa, Laura; Chen, Xuqi; Watkins, Rebecca et al. (2008) Sex chromosome complement affects nociception and analgesia in newborn mice. J Pain 9:962-9
Chen, Xuqi; Watkins, Rebecca; Delot, Emmanuele et al. (2008) Sex difference in neural tube defects in p53-null mice is caused by differences in the complement of X not Y genes. Dev Neurobiol 68:265-73

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