Effect of perinatal HDAC inhibitor administration on sexually dimorphic cell death in the BNST

EK Murray, CJ Smith, A Hien, MM Varnum, GJ De Vries, NG Forger

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

    Abstract

    Sex differences have been identified in relation to many neural characteristics and behaviors. Most sex differences arise following exposure to testosterone, but relatively little is known about the molecular mechanisms of steroid hormone action. In many cases, perinatal hormone exposure determines life-long sex specific changes, suggesting a cellular memory for the testosterone exposure. Testosterone-induced changes in chromatin structure could lead to long-term changes in gene expression and account for this memory. We previously showed that treatment of neonatal mice with the histone deacetylase inhibitor, valproic acid, blocked sexual differentiation of cell number in the bed nucleus of the stria terminalis (BNST). In the present study, we tested the hypothesis that VPA blocked masculinization by altering developmental cell death. To do this, we administered VPA during the critical period for hormone action and determined the number of dying cells during the first week of life using activated caspase-3 immunohistochemistry and TUNEL staining. Females had more dying cells on postnatal days 5 and 6 than males and testosterone treatment decreased the density of TUNEL-positive cells to the level of control males. As expected, VPA treatment had no effect on the number of dying cells in males or control females. VPA did, however, prevent the cell survival associated with testosterone treatment in females. This partially supports the prediction that VPA blocked masculinization of the BNST by altering sexually dimorphic cell death.
    LanguageEnglish
    Title of host publicationUnknown Host Publication
    Number of pages1
    Publication statusPublished - 2010
    EventSociety for Neuroscience, 2010 - San Diego
    Duration: 1 Jan 2010 → …

    Conference

    ConferenceSociety for Neuroscience, 2010
    Period1/01/10 → …

    Fingerprint

    Septal Nuclei
    Histone Deacetylase Inhibitors
    Testosterone
    Cell Death
    Cell Count
    In Situ Nick-End Labeling
    Hormones
    Sex Characteristics
    Sex Differentiation
    Valproic Acid
    Therapeutics
    Caspase 3
    Chromatin
    Cell Survival
    Immunohistochemistry
    Steroids
    Staining and Labeling
    Gene Expression

    Cite this

    Murray, EK., Smith, CJ., Hien, A., Varnum, MM., De Vries, GJ., & Forger, NG. (2010). Effect of perinatal HDAC inhibitor administration on sexually dimorphic cell death in the BNST. In Unknown Host Publication
    Murray, EK ; Smith, CJ ; Hien, A ; Varnum, MM ; De Vries, GJ ; Forger, NG. / Effect of perinatal HDAC inhibitor administration on sexually dimorphic cell death in the BNST. Unknown Host Publication. 2010.
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    abstract = "Sex differences have been identified in relation to many neural characteristics and behaviors. Most sex differences arise following exposure to testosterone, but relatively little is known about the molecular mechanisms of steroid hormone action. In many cases, perinatal hormone exposure determines life-long sex specific changes, suggesting a cellular memory for the testosterone exposure. Testosterone-induced changes in chromatin structure could lead to long-term changes in gene expression and account for this memory. We previously showed that treatment of neonatal mice with the histone deacetylase inhibitor, valproic acid, blocked sexual differentiation of cell number in the bed nucleus of the stria terminalis (BNST). In the present study, we tested the hypothesis that VPA blocked masculinization by altering developmental cell death. To do this, we administered VPA during the critical period for hormone action and determined the number of dying cells during the first week of life using activated caspase-3 immunohistochemistry and TUNEL staining. Females had more dying cells on postnatal days 5 and 6 than males and testosterone treatment decreased the density of TUNEL-positive cells to the level of control males. As expected, VPA treatment had no effect on the number of dying cells in males or control females. VPA did, however, prevent the cell survival associated with testosterone treatment in females. This partially supports the prediction that VPA blocked masculinization of the BNST by altering sexually dimorphic cell death.",
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    Murray, EK, Smith, CJ, Hien, A, Varnum, MM, De Vries, GJ & Forger, NG 2010, Effect of perinatal HDAC inhibitor administration on sexually dimorphic cell death in the BNST. in Unknown Host Publication. Society for Neuroscience, 2010, 1/01/10.

    Effect of perinatal HDAC inhibitor administration on sexually dimorphic cell death in the BNST. / Murray, EK; Smith, CJ; Hien, A; Varnum, MM; De Vries, GJ; Forger, NG.

    Unknown Host Publication. 2010.

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

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    T1 - Effect of perinatal HDAC inhibitor administration on sexually dimorphic cell death in the BNST

    AU - Murray, EK

    AU - Smith, CJ

    AU - Hien, A

    AU - Varnum, MM

    AU - De Vries, GJ

    AU - Forger, NG

    PY - 2010

    Y1 - 2010

    N2 - Sex differences have been identified in relation to many neural characteristics and behaviors. Most sex differences arise following exposure to testosterone, but relatively little is known about the molecular mechanisms of steroid hormone action. In many cases, perinatal hormone exposure determines life-long sex specific changes, suggesting a cellular memory for the testosterone exposure. Testosterone-induced changes in chromatin structure could lead to long-term changes in gene expression and account for this memory. We previously showed that treatment of neonatal mice with the histone deacetylase inhibitor, valproic acid, blocked sexual differentiation of cell number in the bed nucleus of the stria terminalis (BNST). In the present study, we tested the hypothesis that VPA blocked masculinization by altering developmental cell death. To do this, we administered VPA during the critical period for hormone action and determined the number of dying cells during the first week of life using activated caspase-3 immunohistochemistry and TUNEL staining. Females had more dying cells on postnatal days 5 and 6 than males and testosterone treatment decreased the density of TUNEL-positive cells to the level of control males. As expected, VPA treatment had no effect on the number of dying cells in males or control females. VPA did, however, prevent the cell survival associated with testosterone treatment in females. This partially supports the prediction that VPA blocked masculinization of the BNST by altering sexually dimorphic cell death.

    AB - Sex differences have been identified in relation to many neural characteristics and behaviors. Most sex differences arise following exposure to testosterone, but relatively little is known about the molecular mechanisms of steroid hormone action. In many cases, perinatal hormone exposure determines life-long sex specific changes, suggesting a cellular memory for the testosterone exposure. Testosterone-induced changes in chromatin structure could lead to long-term changes in gene expression and account for this memory. We previously showed that treatment of neonatal mice with the histone deacetylase inhibitor, valproic acid, blocked sexual differentiation of cell number in the bed nucleus of the stria terminalis (BNST). In the present study, we tested the hypothesis that VPA blocked masculinization by altering developmental cell death. To do this, we administered VPA during the critical period for hormone action and determined the number of dying cells during the first week of life using activated caspase-3 immunohistochemistry and TUNEL staining. Females had more dying cells on postnatal days 5 and 6 than males and testosterone treatment decreased the density of TUNEL-positive cells to the level of control males. As expected, VPA treatment had no effect on the number of dying cells in males or control females. VPA did, however, prevent the cell survival associated with testosterone treatment in females. This partially supports the prediction that VPA blocked masculinization of the BNST by altering sexually dimorphic cell death.

    M3 - Conference contribution

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    ER -

    Murray EK, Smith CJ, Hien A, Varnum MM, De Vries GJ, Forger NG. Effect of perinatal HDAC inhibitor administration on sexually dimorphic cell death in the BNST. In Unknown Host Publication. 2010