Estrogen fluctuations reshape brain connections, new study finds

A new study out of the University of Delaware shows that fluctuations in estrogen influence the brain, helping reshape connections between neurons. Researchers showed that a specialized imaging technique called magnetic resonance elastography (MRE) can detect estrogen-dependent mechanical changes in the hippocampus, a brain region involved in memory and learning, across the reproductive cycle.

The findings, published in Brain Communications, lay the groundwork for future studies exploring how hormonal changes, including long-term transitions like menopause, affect brain health in women.

"Across the reproductive cycle, the brain adapts, relying more heavily on different regions at different times. This was step one: can we track these changes with MRE in rats, and then eventually in humans?" said first author Katrina Milbocker, a postdoctoral researcher in Curtis Johnson's laboratory and a UD alumna with a doctorate in behavioral neuroscience.

"Imaging is often viewed as a tool for detecting disease, but it can also help us understand brain health dynamically," said Johnson, an associate professor of biomedical engineering. "Our ultimate goal is to understand how brain mechanics change across life stages and what those changes can tell us about health and aging."

Toward clinical translation 

While the study links hormone fluctuations to changes in hippocampal mechanics, the question of whether those changes influence brain function remains. A key next step is connecting MRE measurements with cognition, including memory and learning.

Johnson's team is also extending the work into rat models of menopause, a life stage in which the body produces much lower levels of estrogen. "We suspect there may be a mechanical 'stuck state' when estrogen is first depleted, contributing to disrupted cognitive function like brain fog, and we are trying to test this next," he said.

At the same time, the team is working to translate the findings to humans through parallel rodent and human studies.

"One unique advantage at UD is that the human and animal imaging facilities are in the same building, which makes collaboration easier," Milbocker said.

Ultimately, they hope to make MRE fast enough to be incorporated into routine MRI exams, ideally adding less than a minute to a standard scan.

"Transitions such as menopause span years, and we want to understand how brain health changes across them and how to support individuals during those periods," Johnson said.