Brain estrogen loss linked to memory problems in old female mice
Experiments in mice aged 6 to 8 months and over 19 months linked low brain estrogen to memory difficulties and altered gene activity in older females.
Limit: Gene-activity analysis used three mice per group
Edited by Boris Djordjevic · AgingResearch.News
In an animal experiment, researchers studied male and female mice aged 6 to 8 months or over 19 months. They compared controls with mice whose gene for aromatase, an enzyme needed to make estrogen, had been deleted either in the brain or throughout the body.
Only older females in both groups showed impaired spatial working memory—remembering recently visited locations—and social interaction. Females lacking aromatase throughout the body also showed depression-like behavior at both ages; males did not. In older females lacking brain aromatase, researchers found increased activity of genes linked to the extracellular matrix, the material surrounding cells. These changes occurred in the hippocampus, a brain region involved in memory. The authors linked local brain estrogen deficiency to these molecular changes alongside memory and behavioral difficulties.
Why it matters
Estrogen made within the brain may be relevant to why vulnerability to Alzheimer’s disease differs by sex and age.
Caveats
The behavioral tests measured memory and depression-like behavior in mice, not Alzheimer’s disease or depression in people. Gene-activity analysis used three mice per group, and protein measurements did not consistently match the gene-activity changes.
- CYP19A1
- Extracellular matrix
- Extracellular matrix remodeling
- Brain estrogen
- Depression-like behavior
- Mice
The paper
Northwestern University
Aging Cell, May 26, 2026, Open access
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