Individual’s face increasing societal pressure in the context of a “have it all” culture. Additionally, women undergo unique molecular transformations throughout life, such as the menopause, which can significantly impact brain function and overall well-being. Notably, menopause can give rise to various brain-related symptoms, including memory problems, mood swings, sleep disturbances, fatigue and decreased libido.
This PhD project aims to address three key questions:
Objective 1. Can microglia vesicles be detected and accurately measured in blood samples?
Objective 2. Do molecules in microglia vesicles or vesicles in blood (membrane and cargo) provide insights into well-being and sleep?
Objective 3. How do molecular changes in vesicles relate to well-being during the menopause?
This study will first develop a method targeting brain vesicles, using a protocol with blood samples from healthy individuals. The technology will be a first of its kind, and so far only demonstrated in brain tissue. The primary focus is to detect neuroactive molecules found within microglia vesicles, proxi of brain mechanisms. Examples of these molecules are endocannabinoids, molecules that have been defined as “happy molecules” such as anandamide or “insomnia molecules” such as oleamide. Our previous research has shown associations between the levels of oleamide in blood and amyloid in the brain (1) and detected oleamide in vesicles from rodent microglia (2). Mass spectrometry omics can detect many molecules in vesicles, and we will aim to map their molecular cargos. As a proof of concept, to identify neuroactive molecules that play key roles during menopause, a small cohort of post-menopausal women with and without insomnia symptoms will be recruited and phenotyped (n=20).