Central Nervous System-Specific Knockout of Steroidogenic Factor 1 Results in Increased Anxiety-Like Behavior
| Autor: | Liping Zhao, Stuart A. Tobet, Laurel Beck, Keith L. Parker, Kimberly K. Anderson, Yayoi Ikeda, Ki Woo Kim, Stephanie Chase |
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| Rok vydání: | 2008 |
| Předmět: |
Central Nervous System
Steroidogenic factor 1 medicine.medical_specialty Central nervous system Hypothalamus Anxiety Biology Steroidogenic Factor 1 Receptors Corticotropin-Releasing Hormone Article Mice Endocrinology Neurotrophic factors Internal medicine Chlorocebus aethiops medicine Animals Promoter Regions Genetic Receptor Molecular Biology Mice Knockout Brain-derived neurotrophic factor Regulation of gene expression Binding Sites Behavior Animal Brain-Derived Neurotrophic Factor General Medicine Mice Inbred C57BL medicine.anatomical_structure Animals Newborn Gene Expression Regulation Nuclear receptor Organ Specificity COS Cells |
| Zdroj: | Molecular Endocrinology. 22:1403-1415 |
| ISSN: | 1944-9917 0888-8809 |
| DOI: | 10.1210/me.2008-0034 |
| Popis: | Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor. |
| Databáze: | OpenAIRE |
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