RT Journal Article
SR Electronic
T1 Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0132-17.2018
DO 10.1523/ENEURO.0132-17.2018
VO 5
IS 6
A1 Lauren Broestl
A1 Kurtresha Worden
A1 Arturo J. Moreno
A1 Emily J. Davis
A1 Dan Wang
A1 Bayardo Garay
A1 Tanya Singh
A1 Laure Verret
A1 Jorge J. Palop
A1 Dena B. Dubal
YR 2018
UL http://www.eneuro.org/content/5/6/ENEURO.0132-17.2018.abstract
AB Alzheimer’s disease (AD) begins several decades before the onset of clinical symptoms, at a time when women may still undergo reproductive cycling. Whether ovarian functions alter substrates of AD pathogenesis is unknown. Here we show that ovarian cycle stages significantly modulate AD-related alterations in neural network patterns, cognitive impairments, and pathogenic protein production in the hAPP-J20 mouse model of AD. Female hAPP mice spent more time in estrogen-dominant cycle stages and these ovarian stages worsened AD-related network dysfunction and cognitive impairments. In contrast, progesterone-dominant stages and gonadectomy attenuated these AD-related deficits. Further studies revealed a direct role for estradiol in stimulating neural network excitability and susceptibility to seizures in hAPP mice and increasing amyloid beta levels. Understanding dynamic effects of the ovarian cycle on the female nervous system in disease, including AD, is of critical importance and may differ from effects on a healthy brain. The pattern of ovarian cycle effects on disease-related networks, cognition, and pathogenic protein expression may be relevant to young women at risk for AD.