Project description
New insights into menstrual migraine mechanisms
Females endure three times more migraine attacks than males, with menstrual migraines affecting 60 % of women, severely affecting their lives due to oestrogen withdrawal. However, understanding these migraines remains elusive, hindering innovative treatments. With the support of the Marie Skłodowska-Curie Actions programme, the NET project aims to decipher the mysteries of menstrual migraines through advanced research on oestrogen-related molecular changes in cerebrovascular function and translating these insights into a precise migraine model, offering hope for effective treatments. The project will delve deep into rodent cardiovascular reactivity throughout the estrous cycle, focusing on Kv7 subcellular trafficking via the novel G-protein coupled oestrogen receptor, GPER1.
Objective
Females experience 3 times more migraine attacks than males, with menstrual migraine affecting 60% of these females. They occur before or during menses and are associated with oestrogen (E2) withdrawal, dramatically affecting a patients quality of life. Menstrual migraines are poorly understood, limiting novel treatment strategy discovery. Recently, I demonstrated that E2 withdrawal increases the function and forward membrane trafficking of specific potassium channels (Kv7) in systemic arteries. If present within the cerebrovascular system, E2 withdrawal will increase sensitivity to endogenous migraine-inducing vasodilators, such as calcitonin gene-related peptide (CGRP), contributing to migraine onset.
This project is split into two objectives. 1.) Investigate oestrus cycle-dependent changes in rodent cerebrovascular reactivity via molecular, functional and electrophysiological techniques, with a focus on E2 mediated changes in Kv7 subcellular trafficking via novel G-protein coupled oestrogen receptor, GPER1. 2.) Translate pre-clinical basic science research generated in objective 1 into a model of mensural migraine. International collaboration with Prof. Geoffrey Abbott at the University of California, Irvine, allows for access to in vivo Hemodynamic Perturbation Monitoring (HPM) and a novel CRISPR/Cas9 Kv7 knockout rat. HPM allows for simultaneous measurement of cerebral blood flow and migraine onset (induced by CGRP). We will investigating if female rats are more susceptible to migraine induction when E2 is low, and and whether they are protected from migraine induction by GPER1 stimulation or Kv7 knockout.
Our project has the potential to reveal novel pathophysiological mechanisms underlying menstrual migraine allowing the development of novel precision treatment strategies. My hosts and I are experts in the field of vascular Kv7 physiology, and are the ideal candidates to carry out this project.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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- natural sciences biological sciences biochemistry biomolecules
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2022-PF-01
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1165 KOBENHAVN
Denmark
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