Neuroscience in Denmark


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General information

Name (center, department, group or other)
Department of Neurobiology Research, University of Southern Denmark (MEYER GROUP)
Contact name
Morten Meyer
Contact email
mmeyer#at#health#dot#sdu#dot#dk
Contact title
Associate Professor
Date
3. May 2017
(Last edited: 3. May 2017)

Brief description of research activities

Our research group is a subgroup within a larger, internationally recognized research unit, with strong international and industrial relations, focusing on injury, protection and repair of CNS nerve cells and glial cells using in vitro and animal models of disease.

The major effort of our group is devoted to harnessing and manipulating the differentiation potential of human neural stem cells and induced pluripotent stem cells. Our research program is focused on identifying molecular and biochemical signals regulating cell fate decisions. We place particular emphasis on formation of functional dopaminergic neurons with midbrain char-acteristics - the cell type that degenerates in Parkinsonís disease.

Using stem cells and dopaminergic neurons derived from developing human brain tissue (neural stem cells) and patients with sporadic or familial Parkinsonís disease (induced pluripotent stem cells), our main current effort is on:

a) investigation of the early cellular changes that underlie the onset of neurodegeneration in familial Parkinsonís disease (cells with and without PARK2 muations). This includes the use of isogenic stem cells in combination with molecular assays and advanced mass spectometry-based methods (proteomics, metabolomics and lipidomics - including post-translational modifications).

b) validation of stem cell-derived human dopamine neurons in a hemiparkinsonian rat model of Parkinsonís disease. This includes long-term survival of transplanted cells to assess cell fate, maturation and integration, as well as functional behavioural assessment for graft function.

Our general ambitions are to advance the understanding of the molecular mechanisms underlying Parkinsonís disease and to contribute to the development of a potential future stem cell therapy.


Keywords

Neurodegeneration and repair, cell transplantation, Parkinson's disease, neural stem cells, induced pluripotent stem cells, dopaminergic differentiation, behavioral assessment

Research tools and techniques

Human neural stem cell lines and induced pluripotent stem cell lines (Parkinson patient/controls)
3-D neurosphere cultures and organotypic brain slice cultures
Animal models of Parkinsonís disease, stereotactic cell transplantation and behavioral analyses
Multiplex cytokine analysis


Scientific Personnel

No of Associate Professors/Postdocs: 2
No of PhD students: 4
Other: 10

Key references from within the last 5 years

Jensen P., Heimberg M., Ducray A.D., Widmer H.R., Meyer M. (2013). Expression of Trefoil factor 1 in the developing and adult rat ventral mesencephalon (PLoS ONE, DOI 10.1371/journal.pone.0076592).

Krabbe C., Thornby Bak S., Linstow C.U., Jensen P., Martinez-Serrano A., Hansen C., Meyer M. (2014). Influence of oxygen tension on dopaminergic differentiation of human fetal stem cells of midbrain and forebrain origin (PLoS ONE. DOI 10.1371/journal.pone.0096465).

Erichsen J.L., Blaabjerg M., Bogetofte H., Martinez Serrano A., Meyer M. (2015). Group I Metabotropic Glutamate Receptors: A Potential Target for Regulation of Proliferation and Differentiation of an Immor-talized Human Neural Stem Cell Line (Basic & Clinical Pharmacology & Toxicology, 116, 4, 329-336).

Jensen P., Ducray A.D., Widmer H.R., Meyer M. (2015). Effects of forskolin on trefoil factor 1 expression in cultured ventral mesencephalic dopaminergic neurons (Neuroscience: DOI 10.1016/ j.neuroscience. 2015.10.010).

Clausen B.H., Degn M., Sivasaravanaparan M., Fogtmann T., Andersen M.G., Trojanowsky M.D., Gao H., Hvidsten S., Baun C., Deierborg T., Finsen B., Kristensen B.W., Bak S.T., Meyer M., Lee J., Nedospasov S.A., Brambilla R., Lambertsen K.L. (2016). Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling (Science Reports, DOI 10.1038/srep29291).

Momcilovic O., Sivapatham R., Oron T.R., Meyer M., Mooney S.D., Rao M., Zeng X. (2016). Derivation, characterization, and neural differentiation of integration-free induced pluripotent stem cell lines from Parkinsonís disease patients carrying SNCA, LRRK2, PARK2, and GBA mutations (PLoS ONE, DOI 10.1371/journal.pone.0154890).

Holmqvist S., Lehtonen ä., Chumarina M., Puttonen K.A., Azevedo C., Lebedeva O., Ruponen M., Oksanen M., Dejlloul M., Collin A., Goldwurm S., Meyer M., Lagarkova M., Kiselev S., Koistinaho J., Roybon L. (2016). Creation of a library of induced pluripotent stem cell models from Parkinsonian patients (NPJ Par-kinsonís Disease, DOI 10.1038/npjparkd.2016.9).

Nielsen M.M.B., Lambertsen K.L., Clausen B.H., Meyer M., Bhandari D.R., Larsen S.T., Poulsen S.S., Spengler B., Janfelt C., Hansen H.S. (2016) Mass spectrometry imaging of biomarker lipids for phagocyto-sis and signalling during focal cerebral ischaemia (Scientific Reports, 6:39571. DOI: 10.1038/srep39571).

Reinert L.S., LopuönŠ K., Winther H., Sun C., Thomsen M.K., Nandakumar R., Mogensen T.H., Leib D.A., Meyer M., Vśgter C, Nyengaard J.R., Fitzgerald K.A., Paludan S.R. (2016). Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defense in the CNS (Nature Communications, 7:13348, DOI 10.1038).

Zhang Y., Schmid B., Nikolaisen N.K., Rasmussen M.A., Aldana B.I., Agger M., Calloe K., Stummann T.C., Larsen H.M., Nielsen T.T., Huang J., Xu F., Liu X., Bolund L., Meyer M., Bak L.K., Waagepetersen H.S., Lou Y., Nielsen J.E., Thre FReJA Consortium, Holst B., Clausen C., Hyttel P., Freude K.K (2017). Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B (Stem Cell Reports, DOI: http://dx.doi.org/10.1016/j.stemcr.2017.01.012).

Perez-Bouza, A., Di Santo, S., Seiler, S., Meyer, M., Andereggen, L., Huber, A., Guzman, R., Widmer, H. R. (2017). Simultaneous transplantation of fetal ventral mesencephalic tissue and encapsulated genetically modified cells releasing GDNF in a hemi-parkinsonian rat model of Parkinson's disease (Cell Transplantation, DOI: 10.3727/096368917X694679).

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