Males and females differ in the regulation and engagement of, but not requirement for, protein degradation in the amygdala during fear memory formation
| Autor: | Madison O'Donnell, Emmarose L. McCoig, Sabrina A. Orsi, Kiley Martin, Shaghayegh Navabpour, Jacob L. Nelsen, Madeline Musaus, Timothy J. Jarome, Hannah Kugler, Rishi K Devulapalli, Taylor McFadden, Natalie Jones, Kayla Farrell |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Ribosomal Proteins medicine.medical_specialty Proteasome Endopeptidase Complex Cognitive Neuroscience Protein subunit Experimental and Cognitive Psychology Protein degradation Amygdala 050105 experimental psychology Article Epigenesis Genetic 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Sex Factors Ubiquitin Memory Internal medicine Gene expression medicine Animals Learning 0501 psychology and cognitive sciences Fear conditioning Ubiquitins Sex Characteristics biology PSMD14 05 social sciences Fear DNA Methylation Rats medicine.anatomical_structure Endocrinology DNA methylation Proteolysis biology.protein Female Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neurobiol Learn Mem |
| ISSN: | 1095-9564 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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