GoKawiilA largely overlooked space between cells in women’s brains may hold the key to understanding memory loss tied to estrogen decline after menopause, reports a new preclinical Northwestern Medicine study.
Nearly two-thirds of Americans with Alzheimer’s disease (AD) are women, but the reasons why women are more vulnerable are still not fully understood. Scientists have long theorized that the loss of estrogen after menopause may reduce the brain’s natural protection against memory loss and neurodegeneration.
In the new study, the scientists examined young and old male and female mice, with or without loss of brain estrogen, which allowed them to pinpoint the effects specifically relevant to older females. They found estrogen loss, aging and female sex are closely linked to problems in an important but frequently ignored aspect of brain biology called the extracellular matrix (ECM), which is highly abundant in the hippocampus.
“This study tells us that females — but not males — may be uniquely sensitive to loss of brain estrogen at old age, potentially contributing to an increased risk of Alzheimer’s disease,” said corresponding author Dr. Hong Zhao, research professor of obstetrics and gynecology in the division of reproductive science in medicine at Northwestern University Feinberg School of Medicine.
The findings, published in the journal Aging Cell, provide new insight into how estrogen loss may affect the aging female brain and could help explain why women are at higher risk for AD.
“We have provided some of the most compelling evidence that estrogen is so important for memory function and other mood functions in the female brain,” said senior author Dr. Serdar Bulun, chair of the department of obstetrics and gynecology at Feinberg and a Northwestern Medicine physician. “This should motivate clinicians to be more aware of the essential role of estrogen for women’s brains, because once memory is gone, it’s gone.”
Looking in the space between cells
Like the mortar between bricks, the ECM is a network of molecules that fills the spaces between brain cells. It’s important for memory, brain development and brain health, and makes up nearly 20% of the brain’s volume. ECM acts like a supportive scaffold between cells that helps brain cells communicate and function properly.
Scientists have traditionally focused on studying brain cells such as neurons and glial cells and have paid much less attention to the space between the cells. This is the first study to examine estrogen loss in the ECM.
“Our findings will hopefully motivate future studies to better understand how this matrix is altered in postmenopausal women, and how it could potentially induce susceptibility to Alzheimer’s disease,” Zhao said.
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