Males and females differ in the regulation and engagement of, but not requirement for, protein degradation in the amygdala during fear memory formation.
Males and females differ in the regulation and engagement of, but not requirement for, protein degradation in the amygdala during fear memory formation.
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DOI：
10.1016/j.nlm.2021.107404
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发表时间：
2021-04
影响因子：
2.7
通讯作者：
Jarome TJ
中科院分区：
文献类型：
--
作者：
Devulapalli R;Jones N;Farrell K;Musaus M;Kugler H;McFadden T;Orsi SA;Martin K;Nelsen J;Navabpour S;O'Donnell M;McCoig E;Jarome TJ
在过去的十年中，强有力的证据表明，泛素蛋白酶体系统介导的蛋白质降解对于杏仁核中恐惧记忆的形成至关重要。然而，这项工作主要是在男性中完成的，关于女性在恐惧记忆形成过程中是否也需要蛋白质降解的问题尚未得到解答。在这里，我们发现雄性和雌性大鼠在恐惧记忆形成过程中对杏仁核蛋白质降解的参与和调节有所不同，但不需要。雄性大鼠（而非雌性大鼠）在恐惧条件反射后杏仁核细胞核中的蛋白质降解增加。相反，女性杏仁核中总体泛素蛋白酶体活性的基线水平升高。基因表达和 DNA 甲基化分析发现，女性泛素编码基因 Uba52 的基线表达增加，该基因启动子区域的 DNA 5-羟甲基化 (5hmc) 增加，表明女性泛素水平增加所必需的常染色质状态。与此一致的是，持续的 CRISPR-dCas9 介导的杏仁核中 Uba52 和蛋白酶体亚基 Psmd14 的沉默降低了雄性和雌性大鼠的基线蛋白降解水平并损害了恐惧记忆，同时增强了两性杏仁核中的基线蛋白降解，促进了恐惧记忆的形成。这些结果表明，虽然男性和女性都需要杏仁核中的蛋白质降解来形成恐惧记忆，但他们在学习后的基线调节和参与这一过程方面存在差异。这些结果对于理解恐惧记忆形成中性别相关差异的病因具有重要意义。
Over the last decade, strong evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system is critical for fear memory formation in the amygdala. However, this work has been done primarily in males, leaving unanswered questions about whether females also require protein degradation during fear memory formation. Here, we found that male and female rats differed in their engagement and regulation of, but not need for, protein degradation in the amygdala during fear memory formation. Male, but not female, rats had increased protein degradation in the nuclei of amygdala cells after fear conditioning. Conversely, females had elevated baseline levels of overall ubiquitin-proteasome activity in amygdala nuclei. Gene expression and DNA methylation analyses identified that females had increased baseline expression of the ubiquitin coding gene Uba52, which had increased DNA 5-hydroxymethylation (5hmc) in its promoter region, indicating a euchromatin state necessary for increased levels of ubiquitin in females. Consistent with this, persistent CRISPR-dCas9 mediated silencing of Uba52 and proteasome subunit Psmd14 in the amygdala reduced baseline protein degradation levels and impaired fear memory in male and female rats, while enhancing baseline protein degradation in the amygdala of both sexes promoted fear memory formation. These results suggest that while both males and females require protein degradation in the amygdala for fear memory formation, they differ in their baseline regulation and engagement of this process following learning. These results have important implications for understanding the etiology of sex-related differences in fear memory formation.
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影响因子：
7.7
作者：
Jenkins, Edmund Charles;Shah, Nagma;Germain, Doris
通讯作者：
Germain, Doris
性类固醇激素对学习和记忆至关重要：男性和雌性啮齿动物中海马功能的雌激素调节。
DOI：
10.1101/lm.037267.114
发表时间：
2015-09
期刊：
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子：
--
作者：
Frick KM;Kim J;Tuscher JJ;Fortress AM
通讯作者：
Fortress AM
影响因子：
5.3
作者：
Jarome, Timothy J.;Perez, Gabriella A.;Lubin, Farah D.
通讯作者：
Lubin, Farah D.
DOI：
10.1073/pnas.1013063108
发表时间：
2011-02-22
影响因子：
11.1
作者：
Hoeffer, Charles A.;Cowansage, Kiriana K.;Klann, Eric
通讯作者：
Klann, Eric
影响因子：
56.9
作者：
KIM, JJ;FANSELOW, MS
通讯作者：
FANSELOW, MS