School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
Fralin Biomedical Research Institute, Department of Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University, Roanoke, Virginia 24016, USA.
Learn Mem. 2021 Jul 15;28(8):248-253. doi: 10.1101/lm.053429.121. Print 2021 Aug.
Strong evidence supports a role for protein degradation in fear memory formation. However, these data have been largely done in only male animals. Here, we found that following contextual fear conditioning, females, but not males, had increased levels of proteasome activity and K48 polyubiquitin protein targeting in the dorsal hippocampus, the latter of which occurred at chaperones or RNA processing proteins. In vivo CRISPR-dCas9-mediated repression of protein degradation in the dorsal hippocampus impaired contextual fear memory in females, but not males. These results suggest a sex-specific role for protein degradation in the hippocampus during the consolidation of a contextual fear memory.
强有力的证据支持蛋白质降解在恐惧记忆形成中的作用。然而，这些数据主要是在雄性动物中进行的。在这里，我们发现，在进行情境性恐惧条件反射后，雌性动物而非雄性动物的背侧海马体中的蛋白酶体活性和 K48 多聚泛素蛋白靶向增加，后者发生在伴侣蛋白或 RNA 处理蛋白上。在体内，CRISPR-dCas9 介导的背侧海马体中的蛋白质降解抑制会损害雌性而非雄性的情境性恐惧记忆。这些结果表明，在情境性恐惧记忆的巩固过程中，蛋白质降解在海马体中具有性别特异性作用。
