ArticleBiology of sex differences2023
Sex-differences in proteasome-dependent K48-polyubiquitin signaling in the amygdala are developmentally regulated in rats.
Article in Biology of sex differences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Non-canonical K27 polyubiquitination is a sex-specific regulator of contextual fear memory in the hippocampus but not the amygdala.Behavioural brain research · 2026Article
- Reductions in protein degradation in the retrosplenial cortex regulate contextual fear memory formation in a sex-independent manner.Neurobiology of learning and memory · 2026Article
- Age-related dysregulation of proteasome-independent K63 polyubiquitination in the hippocampus and amygdala.Neuroscience · 2025Article
- Nerve injury induces pain hypersensitivity and anxiety-related behaviours and is associated with amygdala activation in male mice.PloS one · 2025Article
- Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.PloS one · 2024Article
- Differential impacts of advanced age and sex in age-related trace fear memory impairment in rats.Learning & memory (Cold Spring Harbor, N.Y.)Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSex differences have been observed in several brain regions for the molecular mechanisms involved in baseline (resting) and memory-related processes. The ubiquitin proteasome system (UPS) is a major protein degradation pathway in cells. Sex differences have been observed in lysine-48 (K48)-polyubiquitination, the canonical degradation mark of the UPS, both at baseline and during fear memory formation within the amygdala. Here, we investigated when, how, and why these baseline sex differences arise and whether both sexes require the K48-polyubiquitin mark for memory formation in the amygdala.
methodsWe used a combination of molecular, biochemical and proteomic approaches to examine global and protein-specific K48-polyubiquitination and DNA methylation levels at a major ubiquitin coding gene (Uba52) at baseline in the amygdala of male and female rats before and after puberty to determine if sex differences were developmentally regulated. We then used behavioral and genetic approaches to test the necessity of K48-polyubiquitination in the amygdala for fear memory formation.
resultsWe observed developmentally regulated baseline differences in Uba52 methylation and total K48-polyubiquitination, with sexual maturity altering levels specifically in female rats. K48-polyubiquitination at specific proteins changed across development in both male and female rats, but sex differences were present regardless of age. Lastly, we found that genetic inhibition of K48-polyubiquitination in the amygdala of female, but not male, rats impaired fear memory formation.
conclusionsThese results suggest that K48-polyubiquitination differentially targets proteins in the amygdala in a sex-specific manner regardless of age. However, sexual maturity is important in the developmental regulation of K48-polyubiquitination levels in female rats. Consistent with these data, K48-polyubiquitin signaling in the amygdala is selectively required to form fear memories in female rats. Together, these data indicate that sex-differences in baseline K48-polyubiquitination within the amygdala are developmentally regulated, which could have important implications for better understanding sex-differences in molecular mechanisms involved in processes relevant to anxiety-related disorders such as post-traumatic stress disorder (PTSD).
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