Menopausal Hormone Changes Linked to Cognitive Deficits

New research links menopause to cognitive deficits and brain atrophy, emphasizing the role of estrogen receptor beta in astrocytes. Findings from female mice studies suggest potential treatments targeting ERβ for improving cognition and reversing brain changes in menopause.

A recent study led by Dr. Rhonda Voskuhl, a neurologist at UCLA, has unveiled significant insights into how menopause contributes to cognitive decline and brain shrinkage, pinpointing the vital influence of estrogen receptor beta (ERβ) in astrocytes.

This research, carried out using female mice, identified the specific brain regions and mechanisms that drive the cognitive alterations observed during menopause.

Estrogen Loss and Cognitive Impairment: Insights from Animal Models

The research found that loss of ovarian hormones in female mice during midlife, but not at a younger age, induced cognitive impairment. This revealed that both aging and loss of estrogen were critical to cognitive deficits.

Additionally, brain MRIs of these midlife female mice demonstrated atrophy of the dorsal hippocampus, a brain region central to memory and learning, and pathology revealed activation of astrocytes and microglia, with synaptic loss.

The Role of Estrogen Receptor Beta in Brain Health

Selective deletion of estrogen receptor beta (ERβ) in astrocytes, a supportive brain cell, had the same detrimental effects on the brain as hormone loss, suggesting that ERβ in astrocytes plays a pivotal role in maintaining hippocampal function during menopause.

To translate their findings to humans, the researchers showed that changes in gene expression in the hippocampus of estrogen-deficient midlife female mice involved abnormal glucose utilization, and expression of a key gene in this pathway also occurred in post-menopausal women.

Potential Treatments for Menopause-Induced Brain Changes

Aiming to prevent the deleterious effects of estrogen deficiency at midlife, mice treated with an ERβ ligand had improved cognition and reversal of the neuropathological changes observed in the dorsal hippocampus.

While further research is needed to translate these findings into clinical applications for human patients, the study marks a significant step toward understanding the brain’s response to hormonal changes during menopause and offers hope for potential treatments in the future. 

Reference: “Estrogen receptor beta in astrocytes modulates cognitive function in mid-age female mice” by Noriko Itoh, Yuichiro Itoh, Cassandra E. Meyer, Timothy Takazo Suen, Diego Cortez-Delgado, Michelle Rivera Lomeli, Sophia Wendin, Sri Sanjana Somepalli, Lisa C. Golden, Allan MacKenzie-Graham and Rhonda R. Voskuhl, 28 September 2023, Nature Communications.
DOI: 10.1038/s41467-023-41723-7

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