L-Serine Influences Epigenetic Modifications to Improve Cognition and Behaviors in Growth Hormone-Releasing Hormone Knockout Mice.
L-Serine Influences Epigenetic Modifications to Improve Cognition and Behaviors in Growth Hormone-Releasing Hormone Knockout Mice.
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DOI：
10.3390/biomedicines11010104
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发表时间：
2022-12-30
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
神经退行性疾病的特征是认知、焦虑样行为和自闭症样行为的改变，这些变化与DNA甲基化和组蛋白修饰等表观遗传改变有关。氨基酸l -丝氨酸已被证明对神经系统症状有有益作用。在这里，我们发现生长激素释放激素敲除（GHRH-KO）小鼠，一种以寿命延长和胰岛素敏感性增强为特征的gh缺乏小鼠模型，表现出较低的焦虑症状，短期物体识别记忆和自闭症样行为的损害。有趣的是，l -丝氨酸在小鼠中发挥了抗焦虑作用，改善了GHRH-KO的行为缺陷。l -丝氨酸处理上调了GHRH-KO小鼠和野生型对照组海马中的H3K4me、H3K9ac、H3K14ac和H3K18ac以及大脑皮层中的H3K4me组蛋白表观遗传标记。l -丝氨酸调节的表观遗传标记改变，进而被发现调节BDNF、grm3、foxp1、shank3、auts2和marksl1 mRNA的表达，这些基因与焦虑、认知和自闭症样行为有关。我们的研究为l -丝氨酸干预对神经心理障碍的有益作用提供了新的见解。
Neurodegenerative diseases feature changes in cognition, and anxiety-like and autism-like behaviors, which are associated with epigenetic alterations such as DNA methylation and histone modifications. The amino acid L-serine has been shown to have beneficial effects on neurological symptoms. Here, we found that growth hormone-releasing hormone knockout (GHRH-KO) mice, a GH-deficiency mouse model characterized by extended lifespan and enhanced insulin sensitivity, showed a lower anxiety symptom and impairment of short-term object recognition memory and autism-like behaviors. Interestingly, L-serine administration exerted anxiolytic effects in mice and ameliorated the behavioral deficits in GHRH-KO. L-serine treatment upregulated histone epigenetic markers of H3K4me, H3K9ac, H3K14ac and H3K18ac in the hippocampus and H3K4me in the cerebral cortex in both GHRH-KO mice and wild type controls. L-serine-modulated epigenetic marker changes, in turn, were found to regulate mRNA expression of BDNF, grm3, foxp1, shank3, auts2 and marcksl1, which are involved in anxiety-, cognitive- and autism-like behaviors. Our study provides a novel insight into the beneficial effects of L-serine intervention on neuropsychological impairments.
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影响因子：
22.4
作者：
Cummings, Colleen M.;Caporino, Nicole E.;Kendall, Philip C.
通讯作者：
Kendall, Philip C.
DOI：
10.1098/rspb.2015.2397
发表时间：
2016-01-27
期刊：
Proceedings. Biological sciences
影响因子：
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作者：
Cox PA;Davis DA;Mash DC;Metcalf JS;Banack SA
通讯作者：
Banack SA
Dnmt1 和 Dnmt3a 维持 DNA 甲基化并调节成人前脑神经元的突触功能
影响因子：
25
作者：
Feng, Jian;Zhou, Yu;Campbell, Susan L.;Le, Thuc;Li, En;Sweatt, J. David;Silva, Alcino J.;Fan, Guoping
通讯作者：
Fan, Guoping
影响因子：
14.8
作者：
Leger, Marianne;Quiedeville, Anne;Freret, Thomas
通讯作者：
Freret, Thomas
影响因子：
10.6
作者：
Hodes GE;Epperson CN
通讯作者：
Epperson CN