ArticleAging cell2026
Loss of Brain-Derived Estrogen Is Associated With Sex- and Age-Dependent Alterations in Memory, Affective Behavior, and Hippocampal Extracellular Matrix Gene Expression.
Article in Aging cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Menopausal insomnia as a modifiable node of dementia risk: Mechanistic insights and intervention strategies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Article
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Authors and funding
13 authors.
Funding
Abstract
Nearly two-thirds of Americans with Alzheimer's disease (AD) are women. Prior research suggested that women with AD have lower brain estrogen levels than those without AD. However, how estrogen deficiency modulates this sex-based difference in AD vulnerability is not well understood. Aromatase, the key enzyme for estrogen biosynthesis, is expressed in both neurons and astrocytes of the brain, including the hippocampus. This study aims to assess the mechanistic link between brain-selective aromatase deficiency and sex-specific AD vulnerability. To achieve this goal, we used brain-specific aromatase knockout (bArKO) and whole-body total aromatase knockout (tArKO) mice of both sexes at young (6- to 8-month-old) and old (> 19-month-old) ages. We found that aromatase deletion decreased brain estrogen levels in bArKO mice and circulating and brain estrogen levels in tArKO mice. Impairment in spatial working memory and social interaction behavior was observed only in old female bArKO and tArKO mice. Both young and old female, but not male, tArKO mice displayed depression-like behavior. Bulk RNA-seq analysis of hippocampal tissues from young and old bArKO mice of both sexes revealed enrichment of extracellular matrix-related pathways and upregulated mRNA and/or protein expression of extracellular matrix-associated genes (e.g., Col1a1, Ccn2, Dcn, and Ogn) in old female bArKO mice compared to littermate control mice. These findings point to a novel link between local brain estrogen deficiency and sex- and age-specific extracellular matrix changes in the hippocampus of old bArKO female mice accompanied by AD-related memory and behavioral impairments.
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Registered trials
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