Format

Send to

Choose Destination
eNeuro. 2018 Dec 14;5(6). pii: ENEURO.0132-17.2018. doi: 10.1523/ENEURO.0132-17.2018. eCollection 2018 Nov-Dec.

Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice.

Author information

1
Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, California 94158.
2
Biomedical Sciences Graduate Program, University of California, San Francisco, California 94158.
3
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158.
4
Neurosciences Graduate Program, University of California, San Francisco, California 94158.

Abstract

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.

KEYWORDS:

Alzheimer’s disease; estrogen; hormones; mice; network; sex

PMID:
30627643
PMCID:
PMC6325547
DOI:
10.1523/ENEURO.0132-17.2018
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center