Researchers at the University of California (CA, USA) have shown that ovarian stages considerably alter Alzheimer’s disease (AD)-related changes in neural network patterns and pathogenic protein production in a female mouse model of AD. The research paper was recently published in eNeuro.
Lauren Broestl, lead author from the University of California, and colleauges found that female hAPP mice spent more time in estrogen-dominant cycle stages, causing cognitive impairments and worsened AD-related network dysfunction. However, progesterone-dominant stages and removal of the reproductive system reduced these AD-related problems.
The researchers found that regardless of the similarities in cycle length and fertility, AD model mice spent a greater proportion of time in high estrogen level stages compared to control mice. It is still unknown whether ovarian functions alter substrates of AD pathogenesis.
The study proposed that during the reproductive life-stage pathophysiological changes could occur in the brain. The pattern of ovarian cycle effects on pathogenic protein expression, cognition and disease-related networks could be relevant to young women at risk for AD. This suggested that the reproductive cycle could provide a new window into AD risk among young women.
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In further studies, the team also discovered that in hAPP mice, estradiol has a direct role in stimulating neural network susceptibility and excitability to seizures. The research team believes it is of crucial importance to understand the dynamic effects of the reproductive cycle on the female nervous system in disease, and they could differ from effects on a healthy brain.
Through investigating brain function across the ovarian cycle it could reveal patterns in the brain at risk for AD compared to normal aging. In future this work could open the door for preventative therapies and early treatment for women at risk of developing AD.
Sources: Broestl L, Worden K, Moreno AJ et al. Ovarian cycle stages modulate Alzheimer’s-related cognitive and brain network alterations in female mice. eNeuro doi:10.1523/ENEURO.0132-17.2018 (2018); www.eurekalert.org/pub_releases/2018-12/sfn-rcm112718.php