Project ID NS-MH2024_42

ThemeNS-MH

Co Supervisor 1A Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, Institute of Pharmaceutical ScienceWebsite

Co Supervisor 1B Faculty of Life Sciences & Medicine, School of Life Course & Population Sciences, Department of Nutritional SciencesWebsite

Brain vesicles, a window into cognitive health and well-being

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).

Representative Publications

Kim et al. Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer’s Disease biomarker discovery cohort. Alzheimers Dement. 4: 2019; Featured Article. https://alz-journals.onlinelibrary.wiley.com/doi/10.1016/j.jalz.2019.03.004

Gomez-Pascual et al. Multiomics machine learning identifies sleep and inflammation molecular pathways in prodromal Alzheimer’s Disease. MedRxiv 2023, https://www.medrxiv.org/content/10.1101/2023.03.02.23286674v1

Wood et al. Wild Blueberry (Poly)phenols can Improve Vascular Function And Cognitive Performance In Healthy Older Males And Females: A Double-Blind Randomized Controlled Trial. Am J Clin Nutr 2023 117:6, P1306-1319, JUNE 2023. https://doi.org/10.1016/j.ajcnut.2023.03.017

Barfoot, et al. Effects of daily consumption of wild blueberry on cognition and urinary metabolites in school-aged children: a pilot study’, Eur J Nutr 2021 60:8, pp. 4263-4278. https://doi.org/10.1007/s00394-021-02588-y