| Institute of Biology II | |
| Principal investigator | Prof. Dr. Jörg Mey |
| Graduate students | Kristina Klinkhammer, Sabien van Neerven, Julia Bockelmann |
| Undergraduate students | Andrei Nemes, René König, Milena Stillfried, Dhana Wolf |
| Collaborations | Dr. P. McCaffery, University of Aberdeen, UK Bert Joosten, Uni Maastricht Gary Brook, Department of Neuropathologie, RWTH Cordian Beyer, Neuroanatomy Department, RWTH R&R Incorporated, Tokyo, Japan |
We discovered that the transcriptional activator retinoic acid (RA) participates in the physiological reactions after lesions of the central nervous system and that RA regulates gene expression during peripheral nerve regeneration. Our projects now focus (1) on the regulation and (2) on the physiological functions of the RA signaling system after spinal cord and peripheral nerve injury. |
 Crush lesion of the rat sciatic nerve is used as a model to study cellular and molecular processes of peripheral nerve regeneration in vivo [Zhelyaznik and Mey, 2006] |
 Retinoic acid signal transduction [Mey, 2006] |
Retinoic acid signaling. Retinoic acid receptors act as ligand-activated transcription factors. The local activity of RA is controlled by synthesizing aldehyde dehydrogenases, retinoid binding proteins and degrading enzymes of the cytochrome p450 family. We are investing the regulation of these factors and their interactions with other intracellular signaling pathways. Various primary cultures, e.g. of Schwann cells, astrocytes and neurons, are established in the lab. Regulatory functions of RA are analyzed on the molecular level. |
Regeneration in the nervous system. Retinoids and related molecules appear to regulate inflammatory processes, glial reactions, cell differentiation and axonal growth. These functions are being studied in the context of spinal cord contusion injury and during sciatic nerve regeneration. We are also manipulating the RA signal transduction to develop therapeutic strategies for CNS injury. In addition, we are interested in understanding the role of retinoids as regulators of plastic processes in normal physiology of the brain. |
 Retinoic acid-regulated gene expression is induced by a peripheral nerve crush. Blue staining indicates expession of RAREhspLacZ reporter gene in the regenerating sciatic nerve of a transgenic mouse [Zhelyaznik et al., 2003] |
 Retinoic acid synthesizing cells after spinal cord injury in the rat: NG2 immunoreactive glia cells near the lesion site express the aldehyde dehydrogenase RALDH2 (black dots in the longitudinal spinal cord section, drawing after 7 dpo) [Mey et al., 2005; Kern et al., 2007] |
 During the first week after spinal cord injury, retinoic acid receptors translocate into the cell nuclei of surviving motorneurons [Schrage et al., 2006] |
Grants
Student projects
We offer projects for Staatsexamensarbeiten and Diplomarbeiten as part of the general research in the lab. Candidates will receive intensive training in biochemistry, cell culture methods, classical techniques of developmental biology, or molecular biology. If interested, contact us via e-mail or drop by to have a look at the lab.
EURON
Jörg Mey is the local coordinator of the European Graduate School for Neuroscience, EURON. We offer Marie Curie fellowships at participating universities in Aachen, Bruxelles, Köln, Leuwen, Liège and Maastricht.
Recent publications (retinoic signaling)
S. van Neerven, E. Kampmann and J. Mey. RAR/RXR and PPAR/RXR signaling in neurological and psychiatric diseases. Progr. Neurobiol., 85 (2008): 433-451.
S. Golz, T. Mühleisen, D. Schulte, J. Mey. Regulation of RALDH-1, RALDH-3 and CYP26A1 by transcription factors cVax/Vax2 and Tbx5 in the embryonic chick retina. Int. J. Dev. Neurosci. 26 (2008): 435-445.
E. Kampmann, S. Johann, S. van Neerven, C. Beyer and J. Mey. Anti-inflammatory effect of retinoic acid on prostaglandin synthesis in cultured cortical astrocytes. J. Neurochem. 106 (2008): 320-332.
S. Johann, E. Kampmann, B. Denecke, S. Arnold, M. Kipp, J. Mey, C. Beyer. Expression of enzymes involved in the prostanoid metabolism by cortical astrocytes after LPS-induced inflammation. J. Mol. Neurosci. 34 (2008): 177-185.
E. Kampmann and J. Mey. Retinoic acid enhances TrkB expression and Erk phosphorylation in the chick retina. Neurosci. Lett. 426 (2007): 18-22.
C. Propping, B. Mönig, H. Luksch and J. Mey. Distribution of the cellular retinoic acid binding protein CRABP-I in the developing chick optic tectum. Brain Res. 1168 (2007): 21-31.
M. Kipp, S. Karakaya, S. Johann, E. Kampmann, J. Mey and C. Beyer. Oestrogen and progesterone reduce LPS-induced expression of TNF-alpha and interleukin-18 in midbrain astrocytes. J. Neuroendocrinol. 19 (2007): 1-4.
S. van Neerven and J. Mey. RAR/RXR and PPAR/RXR signaling in spinal cord injury. PPAR Res. (2007), doi:10.1155/2007/29275.
T. Kuenzel, B. Mönig, H. Wagner, J. Mey and H. Luksch. Characterisation of a primary culture of the embryonic auditory hindbrain of the chicken. Eur. J. Neurosci. 25 (2007): 974-984.
J. Mey, K. Schrage, I. Weßels, I. Vollpracht-Crijns. Effects of inflammatory cytokines IL-1beta, IL-6 and TNFalpha on the intracellular localization of retinoid receptors in Schwann cells, Glia 55 (2007): 152-164.
J. Kern, K. Schrage, G.C. Koopmans, E.A. Joosten, P. McCaffery and J. Mey. Characterization of retinaldehyde dehydrogenase 2 induction in NG2-positive glia after spinal cord contusion injury. Int. J. Dev. Neurosci. 25 (2007): 7-16.
V. Johann, J. Schiefer, C. Sass, J. Mey, G. Brook, A. Krüttgen, C. Schlangen, C. Bernreuther, M. Schachner, M. Dihné, und C. M. Kosinski. Time of transplantation and cell preparation determine neural stem cell survival in a mouse model of Huntington’s disease. Exp. Brain Res. 177 (2007): 458-470.
J. Mey. A new therapeutic target for CNS injury? The role of retinoic acid signaling after nerve lesions. J. Neurobiol. 66 (2006): 757-779.
R. Panteri, J. Mey, N. Zhelyaznik, A. D’Altocolle, A. Del Fà, C. Gangitano, R. Marino, E. Lorenzetto, M. Buffelli and F. Keller. Reelin is transiently expressed in the peripheral nerve during development and is upregulated following nerve injury. Mol. Cell. Neurosci. 32 (2006): 133-142.
R. Heise, J. Mey, M. Neis, Y. Marquardt, S. Joussen, H. Ott, M. Megahed, D. R. Bickers, H. F. Merk und J. M. Baron. Skin retinoid concentrations are modulated by CYP26A1 expression restricted to basal keratinocytes in normal human skin and differentiated 3D-skin models. J. Invest. Dermatol. 126 (2006): 2473-2480.
N. Zhelyaznik und J. Mey. Upregulation of retinoic acid receptor RARalpha, RARbeta and retinoid X receptor RXRalpha after sciatic nerve injury. Neuroscience 141 (2006): 1761-1774.
K. Schrage, G. Koopmans, B. Joosten und J. Mey. Macrophages and neurons are targets of retinoic acid
signaling after spinal cord contusion injury.
Eur. J. Neurosci. 23 (2006): 285-295.
J. Mey, D. Morassutti, G. Brook, G. Koopmans and P. McCaffery. Upregulation of retinoic acid
synthesis following acute spinal cord injury.
Eur. J. Neurosci. 21 (2005): 1555-1568.
S. Golz, C. Lantin and J. Mey. Regulation of BMP-4, Tbx-5, and ephrin-B1 by retinoic
acid in the embryonic chick retina.
Neuroreport 15 (2004): 2751-2755.
P. Dirks, S. Tieding, I. Schneider, J. Mey and R. Weiler. Charterization of retinoic
acid neuromodulation in the carp retina.
J. Neurosci. Res. 78 (2004): 177-185.
J. Mey and P. McCaffery. Retinoic acid signaling in the nervous system of adult vertebrates.
Neuroscientist 10 (2004): 409-421.
N. Zhelyaznik, K. Schrage, P. McCaffery and J. Mey. Activation of retinoic acid signaling
after sciatic nerve injury: upregulation of cellular retinoid binding proteins.
Eur. J. Neurosci. 18 (2003): 1033-1040.
V. Johann, N. Jeliaznik, K. Schrage, and J. Mey. Retinoic acid downregulates the
expression of ciliary neurotrophic factor (CNTF) in rat Schwann cells.
Neurosci.Lett. 399 (2003): 13-16.
J. Mey, R. P. Babiuk, R. Clugston, W. Zhang and J. J. Greer. Retinal
dehydrogenase-2 is inhibited by compounds that induce congenital diaphragmatic hernias
in rodents.
Am. J. Pathol. 162 (2003): 673-679.
Recent Presentations at Research Conferences
Society for Neuroscience, Washington, DC, 14.-19.11.2008.
Tagung der Neurowissenschaftlichen Gesellschaft, 25.-29.03.2009.
FASEB Conference on Retinoids, New Haven, CT, 15.-20.06.2008.
Japanese Symposium on Retinoids, Tokyo, Japan, 23.-24.11.2007.
Mickeln Symposium on Neurodegeneration and CNS Repair, Schloss Mickeln/Düsseldorf,
11.-12.05.2007.
Meeting of the German Neuroscience Society, Göttingen, 29.03.-01.04.2007.
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