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首页> 外文期刊>Endocrinology >Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity
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Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity

机译：沮丧，但并非没有：消除雄性小鼠大脑中的雄激素受体不会影响焦虑或HPA活性的雄激素调节

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We previously found that androgen receptor (AR) activity mediates two effects of T in adult male mice: reduction of anxiety-like behaviors and dampening of the hypothalamic-pituitary-adrenal response to stress. To determine whether brain ARs mediate these effects, we used the Cre/loxP technology seeking to disable AR throughout the central nervous system (CNS). Female mice carrying the floxed AR allele (ARlox) were crossed with males carrying cre recombinase transgene controlled by the nestin promoter (NesCre), producing cre in developing neurons and glia. Among male offspring, four genotypes resulted: males carrying ARlox and NesCre (NesARko), and three control groups (wild types, NesCre, and ARlox). Reporter mice indicated ubiquitous Cre expression throughout the CNS. Nevertheless, AR immunocytochemistry in NesARko mice revealed efficient knockout (KO) of AR in some brain regions (hippocampus and medial prefrontal cortex [mPFC]), but not others. Substantial AR protein was seen in the amygdala and hypothalamus among other regions, whereas negligible AR remained in others like the bed nucleus of the stria terminalis and dorsal periaqueductal gray. This selective KO allowed for testing the role of AR in hippocampus and mPFC. Males were castrated and implanted with T at postnatal day 60 before testing on postnatal day 90-100. In contrast with males with global KO of AR, T still modulated anxiety-related behavior and hypothalamic-pituitary-adrenal activity in NesARko males. These results leave open the possibility that AR acting in the CNS mediates these effects of T, but demonstrate that AR is not required in the hippocampus or mPFC for T's anxiolytic effects.
机译：我们以前发现雄激素受体（AR）的活性介导T对成年雄性小鼠的两种作用：减少焦虑样行为和减轻对压力的下丘脑-垂体-肾上腺的反应。为了确定大脑AR是否介导这些作用，我们使用Cre / loxP技术寻求在整个中枢神经系统（CNS）中禁用AR。携带浮雕的AR等位基因的雌性小鼠（ARlox）与携带由巢蛋白启动子（NesCre）控制的cre重组酶转基因的雄性小鼠杂交，在发育中的神经元和神经胶质细胞中产生cre。在雄性后代中，产生了四种基因型：雄性携带ARlox和NesCre（NesARko），以及三个对照组（野生型，NesCre和ARlox）。记者小鼠在整个中枢神经系统中普遍存在Cre表达。尽管如此，NesARko小鼠的AR免疫细胞化学显示某些大脑区域（海马和内侧前额叶皮层[mPFC]）的AR有效敲除（KO）。在其他区域的杏仁核和下丘脑中观察到大量的AR蛋白，而在其他区域（如纹状体终末床核和导水管周围灰色）中残留的AR则微不足道。这种选择性的KO可以测试AR在海马和mPFC中的作用。男性在出生后60天testing割并植入T，然后在出生后90-100天进行测试。与具有整体KO AR的男性相比，T仍能调节NesARko男性的焦虑相关行为和下丘脑-垂体-肾上腺活动。这些结果为中枢神经系统中的AR介导T的这些作用提供了可能性，但是证明了海马或mPFC不需要AR来抑制T的抗焦虑作用。

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