Florey Department of Neuroscience and Mental Health - Research Publications

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Author: Boon, Wah Chin × End date: 2009 × Start date: 2008 ×

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    Estrogens, Brain, and Behavior: Lessons from Knockout Mouse Models
    Hill, RA ; Boon, WC (THIEME MEDICAL PUBL INC, 2009-05)
    The use of animal models to effectively replicate problems such as hormone deficiencies, neurologic diseases, and brain injury and stroke has certainly made a vast contribution to understanding the neuroprotective effects of estrogen in the brain. Studies using gonadectomy procedures followed by 17beta-estradiol replacement have effectively demonstrated the positive effects that estrogen provides in cognitive performance and memory performance tasks. A major problem with such studies is that local brain aromatase (the estrogen-synthesizing enzyme) may still convert locally produced androgens to estrogens. Hence, such "estrogen-deficient" models may not be completely void of estrogen. The generation of the aromatase knockout (ArKO) and estrogen receptor knockout (ERKO) mouse models has enabled researchers to characterize the effects of complete estrogen deficiency within the brain and hence behavior. This review aims to compare and contrast the results of these various mouse models.
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    Evidence for the existence of an estrogen-responsive sexually dimorphic group of cells in the medial preoptic area of the 129SvEv mouse strain
    Hill, RA ; Simpson, ER ; Boon, WC (NATURE PUBLISHING GROUP, 2008-05)
    The current study describes the presence of sexually dimorphic cell groups within the MPO of the 129SvEv, but not the C57BL/6J strain of mice. We detected galanin-positive clusters of cells located in the MPO of 129SvEv and C57BL/6J mice, with sex differences found only in the 129SvEv strain. Aromatase-positive and dense Nissl-counterstained clusters of cells were identified only in the MPO of 129SvEv mice, but not in the C57BL/6J strain. Furthermore, this study has demonstrated that the volume of these sexually dimorphic cell groups is regulated by estrogen, but not testosterone, as male aromatase knockout mice (which have high levels of testosterone, but no estrogen) show reduced cell group volumes. These structural changes, which occur in an estrogen-deficient state may influence male sexual behaviors.
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    Estrogen deficiency results in apoptosis in the frontal cortex of adult female aromatase knockout mice
    Hill, RA ; Chua, HK ; Jones, MEE ; Simpson, ER ; Boon, WC (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2009-05)
    The aromatase knockout (ArKO) mouse is completely estrogen deficient. We previously detected apoptosis in the hypothalamus of 1 year-old male ArKO mice. This study shows that 12 week-old female ArKO mice display spontaneous apoptosis of pyramidal neurons in the frontal cortex while wild-type (WT) littermates show no signs of apoptosis. Concomitantly, bcl-2 related anti-apoptotic genes are down-regulated whereas the pro-apoptotic gene TRADD is up-regulated in the female ArKO frontal cortex. This phenotype can be rescued by 3-week replacement of 17beta-estradiol. Furthermore, the apoptosis phenotype is exacerbated in 12-15 month-old female ArKO mice, which have 30% less neurons in the frontal cortex and lower brain weights than WT counterparts. These data show that estrogens are essential for the survival of female cortical neurons even in the absence of pathological conditions or external assaults. Our observations also demonstrate the sexually dimorphic susceptibility of neurons to estrogen deficiency.