Mice lacking proSAAS display alterations in emotion, consummatory behavior and circadian entrainment.
Mice lacking proSAAS display alterations in emotion, consummatory behavior and circadian entrainment.
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DOI：
10.1111/gbb.12827
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发表时间：
2022-09
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影响因子：
--
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ProSAAS是一种神经内分泌蛋白，被神经肽处理酶切割成十几种产物，包括BigLEN和PEN肽，它们分别结合和激活GPR171和GPR83受体。以前的研究表明，ProSAAS衍生的多肽参与了体重调节、昼夜节律和焦虑样行为等生理功能。在目前的研究中，我们发现proSAAS基因敲除小鼠在旷场、明暗出现和升高的零迷宫测试中表现出强烈的焦虑样行为。这些突变的小鼠还显示出线索恐惧的减少和恐惧增强的惊吓的损害，这表明ProSAAS衍生的多肽在情绪行为中发挥了重要作用。与野生型对照相比，ProSAAS基因敲除小鼠表现出更少的用水量和尿量。在食物消耗和总能量消耗方面，没有观察到基因型之间的差异。然而，在光-暗周期的光部分，突变体的呼吸交换率升高，表明在此期间脂肪代谢降低。虽然prosaas基因敲除的小鼠表现出正常的昼夜活动模式，但即使长期暴露在持续的黑暗中，它们在暴露于光脉冲时也无法改变它们的生物钟。综上所述，这些结果表明，ProSAAS衍生的多肽可以调节一系列行为，包括情绪、新陈代谢和生物钟的调节。Pcsk1n位于小鼠的X染色体上，ProSAAS蛋白产物被加工成十几种多肽。Pcsk1n的破坏导致表型的改变，表明它在包括情绪、新陈代谢和生物钟调节在内的一系列行为中发挥作用。
ProSAAS is a neuroendocrine protein that is cleaved by neuropeptide‐processing enzymes into more than a dozen products including the bigLEN and PEN peptides, which bind and activate the receptors GPR171 and GPR83, respectively. Previous studies have suggested that proSAAS‐derived peptides are involved in physiological functions that include body weight regulation, circadian rhythms and anxiety‐like behavior. In the present study, we find that proSAAS knockout mice display robust anxiety‐like behaviors in the open field, light–dark emergence and elevated zero maze tests. These mutant mice also show a reduction in cued fear and an impairment in fear‐potentiated startle, indicating an important role for proSAAS‐derived peptides in emotional behaviors. ProSAAS knockout mice exhibit reduced water consumption and urine production relative to wild‐type controls. No differences in food consumption and overall energy expenditure were observed between the genotypes. However, the respiratory exchange ratio was elevated in the mutants during the light portion of the light–dark cycle, indicating decreased fat metabolism during this period. While proSAAS knockout mice show normal circadian patterns of activity, even upon long‐term exposure to constant darkness, they were unable to shift their circadian clock upon exposure to a light pulse. Taken together, these results show that proSAAS‐derived peptides modulate a wide range of behaviors including emotion, metabolism and the regulation of the circadian clock. Pcsk1n is located on mouse chromosome X and the proSAAS protein product is processed into more than a dozen peptides. Disruption of Pcsk1n results in phenotypes suggesting its role in a wide range of behaviors including emotion, metabolism and the regulation of the circadian clock.
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影响因子：
4.4
作者：
Bora, Adriana;Annangudi, Suresh P.;Millet, Larry J.;Rubakhin, Stanislav S.;Forbes, Andrew J.;Kelleher, Neil L.;Gillette, Martha U.;Sweedler, Jonathan V.
通讯作者：
Sweedler, Jonathan V.
影响因子：
4.7
作者：
Berezniuk, Iryna;Rodriguiz, Ramona M.;Fricker, Lloyd D.
通讯作者：
Fricker, Lloyd D.
影响因子：
5.3
作者：
Fricker, LD;McKinzie, AA;Douglass, J
通讯作者：
Douglass, J
影响因子：
7.3
作者：
Gomes I;Bobeck EN;Margolis EB;Gupta A;Sierra S;Fakira AK;Fujita W;Müller TD;Müller A;Tschöp MH;Kleinau G;Fricker LD;Devi LA
通讯作者：
Devi LA
DOI：
10.1073/pnas.79.12.3886
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
FRICKER, LD;SNYDER, SH
通讯作者：
SNYDER, SH