Master’s project Dexmedetomidine-enhanced glymphatic drug delivery

The glymphatic system is a brain cleansing system, active during sleep and anesthesia, that facilitates the flow of cerebrospinal fluid in the brain, where it is responsible for cleansing the brain of metabolic waste that accumulates during wakefulness. The recent discovery of the glymphatic system has opened new opportunities in developing treatments that by enhancing glymphatic flow, reinforce the clearance of neurotoxic aggregates, characteristic to many neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. In addition to brain cleansing, the glymphatic system may be utilized in enhancing the delivery of therapeutics to the brain. A sedative drug and α2-adrenergic agonist dexmedetomidine has recently been shown to stimulate the glymphatic system and thus hold potential in enhancing the delivery of intrathecally administered compounds into the brain, but the optimal dosing and treatment regimen, and its ability to improve waste clearance remain unclear. The main focus of this project is to characterize dose-dependent effects of dexmedetomidine to glymphatic flow by using single-photon emission computerized tomography (SPECT/CT).

SPECT/CT allows for dynamic imaging of cerebrospinal fluid-administered  radiolabeled tracer distribution in an anesthetized rat.
SPECT/CT allows for dynamic imaging of cerebrospinal fluid-administered radiolabeled tracer distribution in an anesthetized rat.

We are looking for a highly motivated master student who is interested in neuroscience and pharmacology, and can spend a minimum of one year working on the project. During the project, you will learn to work with rats and familiarize yourself with SPECT/CT and other molecular imaging methods. The candidate should preferably have taken the FELASA animal course or be willing to take this prior to, or at the beginning of the thesis period. Working on this project, you will gain insight into in vivo methods used to study the glymphatic system and be part of a cutting-edge project in an active and diverse research group. Since the glymphatic system is a relatively recent discovery, and many open questions of its function remain, you also have a great opportunity to adapt the project to your own interests.

 

The project will be performed in the laboratory of Professor Maiken Nedergaard at the University of Copenhagen, which is an ambitious and international research group utilizing multiple state-of-the-art techniques to study the brain. Furthermore, we have an interactive community where everyone is always ready to help or give advice, and many social events are also frequently arranged. The project is led by Associate Professor Tuomas Lilius and done under supervision of Dr. Marko Rosenholm. If you are interested in the project, please send your CV and a short letter of motivation to Tuomas and Marko.

 

For more information

Tuomas Lilius (tuomas.lilius@sund.ku.dk)

Associate Professor, MD

Marko Rosenholm (marko.rosenholm@sund.ku.dk)

Postdoc, PhD (Pharm.)