{
  "abstract": "Although 17β-estradiol (E2) is a critical neuromodulator of hippocampus-dependent memory and synaptic plasticity, the molecular mechanisms underlying these effects remain incompletely understood. Previous studies showed that E2 enhances dorsal hippocampus (DH)-dependent memory consolidation by activating signaling pathways that promote protein synthesis and dendritic spine formation. However, these studies largely overlooked the contribution of protein degradation mediated by the ubiquitin proteasome system (UPS), despite extensive evidence implicating UPS activity in long-term memory and synaptic plasticity. Here, we combined temporally specific dorsal hippocampal infusions of the proteasome inhibitor β-lactone with three-dimensional spine morphometry to examine the role of UPS-mediated protein degradation in E2-induced memory consolidation and CA1 spinogenesis. Immediate post-training bilateral infusion of β-lactone into the DH of ovariectomized female mice blocked E2-induced enhancement of object recognition memory and attenuated E2-associated improvements in spatial memory. Arbor-wide Golgi-based analyses revealed robust E2-induced increases in spine number across the apical dendritic tree and smaller parallel effects within the basal arbor. Segment-level analyses showed that E2 produced the greatest structural changes on tertiary apical dendritic segments, increasing total, mushroom, and thin spine density and enhancing multiple morphometric features, including mushroom spine surface area and head-to-neck ratio. Secondary basal dendritic segments exhibited smaller, more variable changes. Many E2-associated structural effects were attenuated or abolished by β-lactone. Together, these findings provide the first evidence that proteasomal protein degradation contributes to estrogenic enhancement of hippocampus-dependent memory and CA1 dendritic spine remodeling, identifying UPS-mediated protein degradation as a previously unrecognized mechanism regulating estrogenic memory consolidation and structural plasticity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Psychological and Brain Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211",
    "School of Animal Sciences, School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sarah B. Beamish",
      "orcid": "0000-0003-0650-3533"
    },
    {
      "affs": [
        0
      ],
      "name": "Kellie S. Gross",
      "orcid": "0000-0002-4152-5327"
    },
    {
      "affs": [
        0
      ],
      "name": "Rachel K. Kuehn",
      "orcid": "0009-0002-5862-250X"
    },
    {
      "affs": [
        0
      ],
      "name": "Kailey A. Frank",
      "orcid": "0000-0002-4152-5327"
    },
    {
      "affs": [
        0
      ],
      "name": "Elise P. Valentine"
    },
    {
      "affs": [
        1
      ],
      "name": "Timothy J. Jarome",
      "orcid": "0000-0001-9189-8992"
    },
    {
      "affs": [
        0
      ],
      "name": "Karyn M. Frick",
      "orcid": "0000-0002-4237-0208"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3n0ehsphz0k2a.bib",
  "cited_by": 0,
  "doi": "10.1523/jneurosci.0619-26.2026",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735475/",
  "id": "3n0ehsphz0k2a",
  "issns": [
    "0270-6474",
    "1529-2401"
  ],
  "landing_url": "https://doi.org/10.1523/jneurosci.0619-26.2026",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Behavioral/Cognitive"
    ],
    [
      "heading",
      "Research Articles"
    ],
    [
      "openalex",
      "2805|Memory and Neural Mechanisms"
    ]
  ],
  "openalex": "W7221067755",
  "pdf_url": "https://www.jneurosci.org/content/jneuro/early/2026/10/08/JNEUROSCI.0619-26.2026.full.pdf",
  "pmcid": "PMC13735475",
  "pmid": "42855312",
  "published": "2026-10-09",
  "publisher": "Society for Neuroscience",
  "ris": "https://research.draconitic.com/paper/3n0ehsphz0k2a.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:09Z",
      "native_id": "PMC13735475",
      "source": "pmc",
      "url": "https://doi.org/10.1523/jneurosci.0619-26.2026"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2805|Memory and Neural Mechanisms",
      "subfield": "neuroscience"
    }
  ],
  "title": "Estradiol-Dependent Memory and Hippocampal Spine Remodeling Require Proteasomal Protein Degradation",
  "title_text": "Estradiol-Dependent Memory and Hippocampal Spine Remodeling Require Proteasomal Protein Degradation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:09Z",
  "url": "https://research.draconitic.com/paper/3n0ehsphz0k2a",
  "venue": "The Journal of Neuroscience",
  "versions": []
}