Women’s Brain Initiative

Targeted Core Research Portfolio

A key goal of the WBI is to attract highly accomplished investigators from diverse fields, and to encourage them to address important questions related to women’s brain health and sex differences in brain function. The core research program advances this goal by providing experienced physicians and researchers with multi-year support for research projects in areas relevant to the WBI mission.  Three such projects are currently underway, and others have been completed, as summarized below.

For more information, contact Charles Jennings, Executive Director, Women’s Brain Initiative, cgjennings@bwh.harvard.edu

Core projects – current awardees

Pamela Rist, ScD [Bio] and JoAnn Manson, MD, DrPH [Bio]

Division of Preventative Medicine

Novel biomarkers for cognitive function in the COSMOS randomized trial.

Alzheimer’s Disease (AD) and its related dementias affect many more women than men, for reasons that include longer life expectancy and burden of caring for partners with dementia, as well as increased biological susceptibility. This project will examine cognitive changes in a large cohort of older adults, building on the recently completed COSMOS trial, which studied the effects of a cocoa flavanol supplement and a multivitamin-multimineral on health outcomes including cardiovascular disease, cancer, and cognitive function.  Initial results point to a significant cognitive benefit from a daily multivitamin-mulitmineral, an encouraging finding which, if replicated in other populations, could have important implications for public health and prevention of cognitive decline.  The WBI project aims to analyze sex differences in this dataset, and to correlate the cognitive changes with recently developed blood-based markers for AD progression.

Will Renthal, MD, Ph.D [Bio] and Andrea Harriott  MD, PhD [Bio]

Department of Neurology and (Dr Harriott) MGH Neurology

Sex differences in mechanisms that initiate migraine aura. 

Migraine is much more common in women than men, especially during their reproductive years, suggesting a likely contribution of sex hormones.  This project will use a mouse model of migraine with aura, in which a wave of electrical activity spreads slowly across the brain, giving rise to a visual aura and other migraine symptoms.  The investigators will use genetic, electrophysiological and behavioral methods to study the underlying mechanisms of this process in mice, and to understand why female brains (both mice and humans) are more susceptible to the induction of migraine-related activity.

Primavera Spagnolo, MD, PhD [Bio]

Department of Psychiatry 

Endocannabinoid signaling and its effects on the inflammatory response: implication for PTSD and beyond.  

Post-traumatic stress disorder (PTSD) is more prevalent in women, for reasons that are not fully understood.  A possible contributor to this difference is signaling by endocannabinoids, naturally-occurring brain molecules that act on the same receptors that are also targeted by cannabinoid drugs.  Evidence suggests a link between endocannabinoids and inflammatory responses, which may in turn affect brain regions related to fear, anxiety, and other aspects of PTSD.  Dr Spagnolo will take advantage of the large MassGeneral Brigham Biobank repository of patient samples, to study the relationships between endocannabinoids, inflammatory markers, and PTSD symptoms, and to explore how these differ between male and female patients.

Core projects – past awardees

Katherine E. Burdick, PhD

BWH Department of Psychiatry and Mary Horrigan Connors Center for Women’s Health and Gender Biology

Harvard Catalyst BIO

WBI Project — Predictors of Cognitive Impairment in Postmenopausal Women with Major Depression

The central goal of this WBI project is to understand cognitive heterogeneity and identify clinical and biological predictors of both risk of and resilience to cognitive decline. Dr. Burdick and her team aim to provide new insights into the predictors of cognitive decline, help inform novel treatments targeting the prevention of cognitive impairment and improve the lives of the many women suffering from this condition.

Silke Nuber, PhD

Ann Romney Center for Neurological Diseases

Harvard Catalyst BIO

WBI Project— Sex Differences and Dopamine Changes in Parkinson’s Disease

The aim of this WBI project is to identify the factors responsible for the protective advantage of the female sex in Parkinson’s disease. This project leverages a recent discovery by Dr. Dennis Selkoe and colleagues that the αSyn protein occurs normally as a “tetramer” (four units of αSyn wound together), which resists the abnormal αSyn aggregation seen in PD. This project also benefits from the use of a novel mouse model developed by Dr. Nuber, which is based on abolishing the normal αSyn tetramers and thereby triggering the development of a progressive PD-like syndrome.

Ursula Kaiser, MD

BWH Division of Endocrinology, Diabetes and Hypertension

Harvard Catalyst BIO

WBI Project— Endocrine Disruptors and the Expression of MKRN3

Research has shown that women are exposed each day to an average of 100 endocrine disrupting compounds, which may interfere with hormone action. The aim of this WBI project is to explore the effects of specific endocrine disruptors in neuronal cell and mouse models and provide important insights into the potential adverse effects on female health, including precocious puberty, infertility, and metabolic syndrome.

Tanjuja Chitnis, MD

BWH Ann Romney Center for Neurologic Disease

Harvard Catalyst BIO

WBI Project — Role of Endocrine Disruptors in the Initiation of Multiple Sclerosis

This project will investigate the effects of endocrine disruptors on immune cells and their ability to migrate to the brain to cause autoimmune disorders, like MS. Dr. Chitnis and colleagues also will investigate how the interaction of endocrine disruptors with sex hormones may activate immune cells to cause MS.

Laura Holsen, PhD

BWH Department of Psychiatry

Harvard Catalyst BIO

WBI Project— Neuro-cognitive Changes in Obesity: The Role of the Appetite Hormone Ghrelin in Mediating the Relationship between Body Mass Index and Abnormal Brain Structure and Function in Postmenopausal Women

Dr. Holsen and colleagues are examining whether postmenopausal women with and without obesity show different relationships between ghrelin (a hormone linked to eat behavior), cognitive function, and brain activity/structure relationships in regions serving cognition and food intake. The aim is to advance our understanding of the link between obesity and cognitive decline.