Androgens Modulate Structure and Function of the Suprachiasmatic Nucleus Brain Clock
Androgens Modulate Structure and Function of the Suprachiasmatic Nucleus Brain Clock
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DOI：
10.1210/en.2010-1398
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发表时间：
2011-05-01
期刊：
影响因子：
4.8
通讯作者：
Silver, Rae
中科院分区：
文献类型：
--
作者：
Karatsoreos, Ilia N.;Butler, Matthew P.;Silver, Rae
性腺激素可以调节啮齿动物和人类的昼夜节律，雄激素受体高度定位于小鼠视交叉上核（SCN）大脑时钟的核心区域。虽然已知雄激素可以调节其他中枢神经系统隔室的神经可塑性，但雄激素及其受体在中枢神经网络可塑性中的作用尚不清楚。在本研究中，我们通过检测性腺切除术（GDX）对小鼠SCN电路结构及其对光反应的影响，包括诱导时钟基因和行为相移，来探讨雄激素是否会影响小鼠SCN的结构和功能。我们发现GDX后，胶质纤维酸性蛋白升高，突触蛋白synaptophysin和突触后密度95的表达降低。我们还发现GDX对光的分子和行为反应具有相依赖性。在深夜[昼夜节律时间（CT） 21]，与完整（INT）对照相比，GDX增加了光诱导的mPer1表达，但没有增加mPer2表达。相比之下，在早期夜间（CT13.5）， GDX降低了光诱导的mPer2，但对mPer1没有影响。在CT13.5时，GDX动物也比INT动物表现出更大的相延迟。用非芳构化雄激素双氢睾酮治疗GDX动物，可恢复SCN中的胶质纤维酸性蛋白、突触后密度95和突触体素，并恢复分子和行为对光反应的INT模式。总之，这些结果揭示了雄激素在调节小鼠SCN电路中的作用，以及时钟基因表达和光相重置刺激的行为反应的功能后果。（内分泌学152:1970-1978,2011）
Gonadal hormones can modulate circadian rhythms in rodents and humans, and androgen receptors are highly localized within the core region of the mouse suprachiasmatic nucleus (SCN) brain clock. Although androgens are known to modulate neural plasticity in other CNS compartments, the role of androgens and their receptors on plasticity in the SCN is unexplored. In the present study, we ask whether androgens influence the structure and function of the mouse SCN by examining the effects of gonadectomy(GDX) on the structure of the SCN circuit and its responses to light, including induction of clock genes and behavioral phase shifting. We found that after GDX, glial fibrillary acidic protein increased with concomitant decreases in the expression of the synaptic proteins synaptophysin and postsynaptic density 95. We also found that GDX exerts effects on the molecular and behavioral responses to light that are phase dependent. In late night [circadian time (CT) 21], GDX increased light induced mPer1 but not mPer2 expression compared with intact (INT) controls. In contrast, in early night (CT13.5), GDX decreased light induced mPer2 but had no effect on mPer1. At CT13.5, GDX animals also showed larger phase delays than did INT. Treatment of GDX animals with the nonaromatizable androgen dihydrotestosterone restored glial fibrillary acidic protein, postsynaptic density 95, and synaptophysin in the SCN and reinstated the INT pattern of molecular and behavioral responses to light. Together, the results reveal a role for androgens in regulating circuitry in the mouse SCN, with functional consequences for clock gene expression and behavioral responses to photic phase resetting stimuli. (Endocrinology 152: 1970-1978, 2011)