Lundgaard Lab

Research

Brain-wide clearance system

Despite a high level of metabolic activity, the brain does not have a conventional lymphatic system to remove metabolites. The glia-lymphatic (glymphatic) system is a waste removal system that uses the perivascular space of the brain for fluid transport. The glymphatic system is a bulk flow system driven arterial pulsation and results in convective flow in the perivascular spaces. The glymphatic system is most active in the sleep state, where production of cerebrospinal fluid (CSF) is highest and the interstitial space is larger. Solutes as well as peptides such as amyloid beta can be transported in perivascular pathways by the glymphatic system and eliminated to the lymphatic vessels. Accumulation of proteins, such as amyloid beta, is a common feature of neurodegenerative diseases and we believe that the control of the glymphatic system could prevent or curb neurodegenerative diseases. Due to the recent discovery of the glymphatic system, many new discoveries are waiting to be made, including how to effectively manipulate the glymphatic system.

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Discovery of the glymphatic system:

http://stm.sciencemag.org/content/4/147/147ra111.full

Review on the glymphatic system

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636982/

Glymphatic system and delivery of small molecules to the brain

https://www.nature.com/articles/ncomms7807

Astrocytes

Astrocytes are the key regulators of brain homeostasis. Their endfeet processes ensheath the cerebral vasculature and contact thousands of synapses. We are interested in the endfeet of astrocytes, as they form perivascular pathways used by the glymphatic system for fluid transport. Aquaporin 4 (AQP4) water channels in the astrocyte endfeet are crucial for influx of cerebrospinal fluid (CSF) into the brain and clearance of solutes. Besides AQP4 molecular drivers of glymphatic flow remain elusive.

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Neuroimmunology

Similar to the lymphatic system, the glymphatic system connects to lymph nodes in the cervical region. Thus, there is a strong association between glymphatic and immune function. Fluid drains from the brain into meningeal lymphatic vessels, to the nasal mucosa via the cribriform plate, via spinal and cranial nerves, or simply perivenously. Drainage from the brain will mount an immune response in cervical lymph nodes. The idea of the brain being ‘immune privileged’ remains true in the sense that there are much fewer patrolling T cells in the brain e.g. than in the skin. However, meningeal lymphatic vessels and CSF efflux to cervical lymph via the nasal mucosa is understudied in relation to central nervous system immune function.

The Lab

Principal investigator, Dr. Iben Lundgaard, is recipient of a large Wallenberg Foundation starting grant. Over the next 4 years, this grant covers 2 PhD students, 2 postdocs plus technical support and also includes running costs and money for equipment.

Lund University

Lund University was founded in 1666 and currently has 42,000 students. The Department for Experimental Medicine is a modern and vibrant place to work and study. The department counts 60 independent research groups and excellent core facilities. The Wallenberg Foundation has announced that they will fund 10 large starting grants in molecular medicine over the next few years to recruit new group leaders. One of these recruitments was Dr. Iben Lundgaard. The new research groups funded by the Wallenberg Foundation will stimulate the research environment and further expand the growing international environment at Lund University.

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Iben Lundgaard

Early Career

Principal investigator Iben Lundgaard has, during her Master degree in molecular biology, obtained experience from aging lab, Suresh Rattan, Na/K ATPase in Nobel laureate Jens Christian Skou's lab at University of Aarhus and apoptosis and calcium binding proteins in Martin Berchtold’s lab at University of Copenhagen. After a short internship in electrophysiology at University of Copenhagen, Iben started her PhD in the UK.

PhD

Iben Lundgaard did a PhD in neuroscience with Ragnhildur Thora Karadottir and Robin Franklin at University of Cambridge, UK, 2008-2012. The main findings of her PhD thesis were that growth factors neuregulin and BDNF interact with neuronal activity to control myelination and that remyelination after injury is dependent on NMDA receptors.

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Postdoctoral training

Dr. Lundgaard worked with Maiken Nedergaard at University of Rochester where the glymphatic system was discovered. During her time in the Nedergaard lab Dr. Lundgaard gained detailed knowledge on the glymphatic system, see for example the study on delivery of glucose from the CSF to the brain parenchyma via the glymphatic system. After 2 years, Dr. Lundgaard was promoted to assistant professor and stayed for another two and a half years to continue glymphatic research in multiple disease models. A number of projects from the Rochester lab are still on-going and will be continued in the new lab at Lund University.

Collaborators

Collaborations are increasingly important to succeed in science. This lab collaborates with other labs from near and far:


Angela Cenci-Nilsson (Parkinson’s disease), Lund University

Tomas Deierborg (microglia and neuroinflammation), Lund University

Maiken Nedergaard (glymphatic system and astrocytes), Copenhagen University and University of Rochester

Steve Goldman (embryonic and induced pluripotent stem cells), Copenhagen University and University of Rochester

Jeff Huang (remyelination), Georgetown University

Deborah Fowell (immunology), University of Rochester

Job vacancies

The Lundgaard Lab is looking for PhD students and master students to work on glia biology, the glymphatic system and neurodegeneration and a postdoc to work on neuroimmunology.

For more details, please contact iben.lundgaard@med.lu.se.

Lundgaard Lab 1
Lundgaard Lab 2

Bibliography

Spitzer S, Volbracht K, Lundgaard I, Káradóttir RT. Glutamate signalling: A multifaceted modulator of oligodendrocyte lineage cells in health and disease. Neuropharmacology. 2016 Nov;110(Pt B):574-585. doi: 10.1016/j.neuropharm.2016.06.014. Epub 2016 Jun 23. Review. PubMed PMID: 27346208.


Lundgaard I, Lu ML, Yang E, Peng W, Mestre H, Hitomi E, Deane R, Nedergaard M. Glymphatic clearance controls state-dependent changes in brain lactate concentration. J Cereb Blood Flow Metab. 2017 Jun;37(6):2112-2124. doi: 10.1177/0271678X16661202. Epub 2016 Jan 1. PubMed PMID: 27481936.


Gautier HO, Evans KA, Volbracht K, James R, Sitnikov S, Lundgaard I, James F, Lao-Peregrin C, Reynolds R, Franklin RJ, Káradóttir RT. Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors. Nat Commun. 2015 Oct 6;6:8518. doi: 10.1038/ncomms9518. PubMed PMID: 26439639.


Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The Glymphatic System: A Beginner's Guide. Neurochem Res. 2015 Dec;40(12):2583-99. doi: 10.1007/s11064-015-1581-6. Epub 2015 May 7. Review. PubMed PMID: 25947369.


Lundgaard I, Li B, Xie L, Kang H, Sanggaard S, Haswell JD, Sun W, Goldman S, Blekot S, Nielsen M, Takano T, Deane R, Nedergaard M. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism. Nat Commun. 2015 Apr 23;6:6807. doi: 10.1038/ncomms7807. PubMed PMID: 25904018.


Lundgaard I, Osório MJ, Kress BT, Sanggaard S, Nedergaard M. White matter astrocytes in health and disease. Neuroscience. 2014 Sep 12;276:161-73. doi: 10.1016/j.neuroscience.2013.10.050. Epub 2013 Nov 11. Review. PubMed PMID: 24231735.


Lundgaard I, Luzhynskaya A, Stockley JH, Wang Z, Evans KA, Swire M, Volbracht K, Gautier HO, Franklin RJ; Charles Ffrench-Constant, Attwell D, Káradóttir RT. Neuregulin and BDNF induce a switch to NMDA receptor-dependent myelination by oligodendrocytes. PLoS Biol. 2013 Dec;11(12):e1001743. doi: 10.1371/journal.pbio.1001743. Epub 2013 Dec 31. PubMed PMID: 24391468.

Contact

Sölvegatan 19 SE-221 84 Lund, Sweden
Room#: BMC F1135

+46 (0)46 222 06 21

iben.lundgaard@med.lu.se