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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reduction of lipocalin-type prostaglandin D synthase in the preoptic area of female mice mimics estradiol effects on arousal and sex behavior
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Reduction of lipocalin-type prostaglandin D synthase in the preoptic area of female mice mimics estradiol effects on arousal and sex behavior

机译：雌性小鼠视前区脂质运载蛋白型前列腺素D合酶的减少模拟雌二醇对唤醒和性行为的影响

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摘要

In female rodents, sleep and activity levels fluctuate over the estrous cycle. When estradiol (E_2) levels are highest, sleep is reduced whereas locomotion is increased. The preoptic area (POA) is a key site for estrogenic regulation of these functions. However, molecular mechanisms by which E_2 acts to reduce sleep and increase activity are unclear. Recently, we demonstrated a twofold reduction in lipocalin-type prostaglandin D synthase (L-PGDS) transcript levels, after E_2 treatment, in the ventrolateral POA (VLPO), a putative sleep-active nucleus. Catalytic activity of L-PGDS produces PGD2, an endogenous somnogen. Thus, we hypothesized that decreases in PGD_2 in the VLPO may contribute to the generalized arousal mediated by estrogens. To test this, we infused (ⅰ) antisense oligonucleotides (oligos), containing locked nucleic acid moieties (an improved technology), targeted to L-PGDS mRNA, (ⅱ) scrambled sequence control oligos, or (ⅲ) saline vehicle into the VLPO of ovariectomized female mice treated with E_2 or oil. Arousal states and activity levels were assessed in response to a series of sensory stimuli (vestibular, olfactory, and somatosensory). The vestibular stimulus, which was administered first, resulted in the strongest responses and elicited significantly different responses among the groups: all groups in the E_2 cohort demonstrated increases in overall home cage activity and duration of that activity compared with the oil-treated control groups. As predicted from E_2 suppression of L-PGDS transcript levels, the responses of the locked nucleic acid antisense oligo-treated animals from the oil cohort did not differ from the E_2-treated groups, such that they also demonstrated increases in activity and duration of activity compared with their controls. Thus, reducing L-PGDS in the VLPO of oil-treated females mimicked the effect of E_2 on activity and arousal and represents a unique molecular pathway through which E_2 may modulate these functions.
机译：在雌性啮齿动物中，睡眠和活动水平会在发情周期内波动。当雌二醇（E_2）水平最高时，睡眠减少，而运动增加。视前区（POA）是雌激素调节这些功能的关键部位。但是，E_2起到减少睡眠和增加活动的分子机制尚不清楚。最近，我们证明在E_2处理后，腹侧POA（VLPO）（一种假定的睡眠活跃核）中的脂环素型前列腺素D合酶（L-PGDS）转录水平降低了两倍。 L-PGDS的催化活性可产生PGD2（内源性钠盐）。因此，我们假设VLPO中PGD_2的减少可能有助于雌激素介导的广泛唤醒。为了测试这一点，我们将（锁定）含有锁定核酸部分的反义寡核苷酸（寡核苷酸）（针对技术的改进）靶向L-PGDS mRNA，（ⅱ）杂乱的序列控制寡核苷酸或（ⅲ）盐水载体注入了VLPO用E_2或油处理的卵巢切除雌性小鼠的数量。根据一系列感觉刺激（前庭，嗅觉和躯体感觉）评估兴奋状态和活动水平。首先施用的前庭刺激产生最强的反应，并在各组之间引起明显不同的反应：E_2队列中的所有组均显示，与用油治疗的对照组相比，总的笼养活动和该活动的持续时间增加了。如从E_2抑制L-PGDS转录水平所预测的，来自油队列的经锁定核酸反义寡核苷酸处理的动物的反应与E_2处理的组没有不同，因此它们也证明了活性和活性持续时间的增加与他们的控件相比。因此，减少经油处理的女性的VLPO中的L-PGDS可以模仿E_2对活性和唤醒的影响，并代表E_2可以调节这些功能的独特分子途径。

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