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Aishling Kelly






Beth Israel Deaconess Medical Center|Harvard Medical School




Carrie Mahoney, Natalia Machado, Aishling Kelly, Thomas Scammell

Principal Investigator


Influence of Orexin Neurons on Stress Response in a Menopausal Mouse Model


Intensified stress responses in menopausal females and underlying mechanisms have been vastly understudied. Our research addresses the connection to orexin neuronal activity in the context of chronic low estradiol and the effect on stress behavior. Our hypothesis states that low estradiol heightens orexin signaling, exacerbating stress responses. We modulate orexin neuron activity in ovariectomized mice with and without estradiol replacement that experience repeated restraint stress. This allows us to define behaviors under chronically low estradiol and discern the role of orexin neurons in mediating stress responses. The findings of this study include potential treatments for menopausal symptoms utilizing orexin antagonists.

Research Context

This research project is important for advancing our understanding of stress response particularly in the context of neuronal changes during menopause—an aspect of female aging that remains largely unexplored. Examining the effects of chronic low estradiol on orexin neuronal activity and stress behavior in ovariectomized mice allows us to bridge a notable gap in women’s health research. The findings can reveal mechanisms influencing stress responses in menopausal females, shedding light on sex-specific physiological changes. Additionally, pinpointing orexin neurons as potential mediators provides a basis for developing targeted treatments for menopausal symptoms to alleviate heightened stress-related responses.