The Bähr Lab

PD Dr. med. Jochen Weishaupt

phone:

+ 49 - 551 - 39 66715

fax:

+ 49 - 551 - 39 8405

e-mail:

jweisha(at)gwdg.de

Main Research Interest

• Molecular mechanisms of neurodegeneration and pathological protein aggregation
• Mitochondrial cell death pathways
• translational neuroprotective approaches, preclinical development
• In vitro and in vivo models of ALS, PD and "Tauopathies"
• Molecular mechanisms of glioma cell migration
• Clinical focus: Parkinson's disease, Amyotrophic lateral sclerosis, Post-Polio-Syndrome

Original Publications

1. T. Frank, B. Göricke, J.C.M Schlachetzki, K. Meuer, G.P.H. Dietz, M. Bähr, A. Schneider, J.H. Weishaupt. Systemic effects are not required for G-CSF neuroprotection in vivo. Submitted.
2. G: Rohde, P. Kermer, J.C. Reed, M. Bähr, J. H. Weishaupt. Neuron-specific overexpression of the co-chaperone BAG1 in SOD1G93A-transgenic mice. Neuroscience 2008, 157: 844-9.
3. G.P. Dietz, K.V. Stockhausen, B. Dietz, B.H. Falkenburger, P. Valbuena, F. Opazo, P. Lingor, K. Meuer, J.H. Weishaupt, J.B. Schulz, M. Bähr. Membrane-permeable Bcl-xL prevents MPTP-induced dopaminergic neuronal loss in the substantia nigra. J Neurochem 2008, 104: 757-65
4. S. Ganesan, G. Rohde, K. Eckermann, K. Sroka, M.K. Schaefer, C.P. Dohm, P. Kermer, G. Haase, F. Wouters, M. Bähr, J.H. Weishaupt. Mutant SOD1 detoxification mechanisms in intact single cells. Cell Death Differ 2008, 15: 312-21.
5. D. Liebetanz, P.C. Baier, W. Paulus, K. Meuer, M. Bähr, J.H. Weishaupt. A highly sensitive automated complex running wheel test to detect latent motor deficits in the mouse MPTP model of Parkinson's disease. Exp Neurol 2007, 205: 207-13.
6. Meuer K, Suppanz IE, Lingor P, Planchamp V, Göricke B, Fichtner L, Braus GH, Dietz GP, Jakobs S, Bähr M, Weishaupt JH. Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis. Cell Death Differ 2007, 14: 651-61.
7. J. H. Weishaupt, C. Bartels, E. Pölking, J. Dietrich, G. Rohde, B. Poeggeler, N. Mertens, S. Sperling, M. Bohn, G. Hüther, A. Schneider, A. Bach, A.-L. Sirén, R. Hardeland, M. Bähr, K.-A. Nave, H. Ehrenreich. Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res 2006, 41: 313-23
8. G.P.H. Dietz, P.C. Valbuena, B. Dietz, K. Meuer, P. Müller, J.H. Weishaupt, M. Bähr. Application of a blood-brain-barrier-penetrating form of GDNF in a mouse model for Parkinson's disease. Brain Res 2006, 1082: 61-6.
9. K. Meuer, C. Pizer, P. Teismann, C. Krüger, B. Göricke, R. Laage, P. Lingor, K. Peters, J.C.M. Schlachetzki, K. Kobayashi, G.P.H. Dietz, A. Bach, J.B. Schulz, M. Bähr, A. Schneider, J.H. Weishaupt. Granulocyte-colony stimulating factor (G-CSF) is neurorotective in a model of Parkinson's disease. J Neurochem 2006, 97: 675-86
10. J.H. Weishaupt, N. Klöcker, M. Bähr. J. Axotomy-induced early down-regulation of POU-IV class transcription factors Brn-3a and Brn-3b in retinal ganglion cells. J Mol Neurosci, 26: 17-25.
11. E. Kilic1, J.H. Weishaupt1, Ü. Kilic, G. Rohde, B. Yulug, K. Peters, and M. Bähr. The Superoxide Dismutase 1 (SOD1) G93A Mutation Does Not Promote Neuronal Injury After Transient Focal Brain Ischemia And Optic Nerve Transection In Mice. Neuroscience 2004, 128: 359-64. (1) equal contribution
12. J.H. Weishaupt, G. Rohde, E. Pölking, A.-L. Siren, H. Ehrenreich, M. Bähr. Effect of erythropoietin axotomy-induced apoptosis in rat retinal ganglion cells. Invest Opthalmol Vis Sci 2004, 45: 1514-22.
13. S. Jacob, J. Finsterbusch, J. H. Weishaupt, D. Khorram-Sefat, J. Frahm and H. Ehrenreich. Diffusion tensor imaging for long-term follow-up of corticospinal tract degeneration in amyotrophic lateral sclerosis. Neuroradiol 2003, 45: 598-600
14. J.H. Weishaupt, L. Kußmaul, P. Grötsch, A. Heckel, M. Bähr and F. Gillardon. CDK5:A major player during both necrotic and apoptotic neuronal cell death that acts upstream of mitochondrial dysfunction. Mol Cell Neurosci 2003, 2003 24: 489-502.
15. J.H. Weishaupt, R. Diem, P. Kermer, S. Krajewsky, R.C. Reed and M. Bähr. Contribution of caspase-8 to apoptosis of axotomized rat retinal ganglion cells in vivo. Neurobiol Dis 2003, 13: 124-135
16. S. Jakob, B. Poeggeler, J. H. Weishaupt, A. L. Siren, R. Hardeland, M. Bähr and H. Ehrenreich. Melatonin as a candidate compound for neuroprotection in amyotrophic lateral sclerosis (ALS): high tolerability of daily oral melatonin administration in ALS patients. J Pineal Res 2002, 33: 186-7.
17. R. Diem, R. Meyer, J.H. Weishaupt and M. Bähr. Reduction of potassium currents and phosphatidylinositol 3-kinase-dependent AKT phosphorylation by tumor necrosis factor-(alpha) rescues axotomized retinal ganglion cells from retrograde cell death in vivo. J Neurosci 2001, 15: 2058-66.
18. N. Klöcker, P. Kermer, J. H. Weishaupt, M. Labes, R. Ankerhold and M. Bähr. Brain-Derived Neurotrophic Factor-Mediated Neuroprotection of adult Rat Retinal Ganglion cells In Vivo Does Not Exclusively Depend on Phosphatidyl-Inositol-3'-Kinase/Protein Kinase B Signaling. J Neurosci 2000, 20: 6962-6967.
19. G. Nase1, J. Weishaupt1, P. Stern, W. Singer and H. Monyer. Genetic and Epigenetic Regulation of NMDA-Receptor Expression in the Rat Visual Cortex. Eur J Neurosci 1999, 11: 4320-6. (1) equal contribution
20. H.S. Ying, J.H. Weishaupt, M. Grabb, L.M.T. Canzoniero, S.L. Sensi, C.T. Sheline, H. Monyer and D.W. Choi. Sublethal Oxygen-Glukose Deprivation Alters Hippocampal Neuronal AMPA Receptor Expression and Vulnerability to Kainate-Induced Death. J Neurosci 1997, 17: 9536-9544.
21. A.C. Flint, U.S. Maisch, J.H. Weishaupt, A.R. Kriegstein and H. Monyer. NR2A Subunit Expression Shortens NMDA Receptor Synaptic Currents in Developing Visual Cortex. J Neurosci 1997, 17: 2469-2476

Review Articles:

1. L. Tönges , J.C.M. Schlachetzki, J.H. Weishaupt, M. Bähr. Hematopoietic cytokines--on the verge of conquering neurology. Curr Mol Med 2007, 7:157-70
2. P. Kermer, J. Liman, J.H. Weishaupt, M. Bähr. Neuronal apoptosis in neurodegenerative diseases: From basic research to clinical application and back. Neurodegenerative diseases 2004, 1: 1-9.
3. J.H. Weishaupt, C. Neusch and M. Bähr. Cyclin dependent kinase 5 (CDK5) and neuronal cell death. Cell Tissue Res 2003, 312: 1-8.
4. C. Neusch, J.H. Weishaupt and M. Bähr. Kir channels in the CNS: Emerging new roles and implications for neurological diseases. Cell Tissue Res 2003, 311: 131-8.
5. P. Kermer, N. Klöcker, J.H. Weishaupt and M. Bähr. Transection of the optic nerve in rats: studying neuronal death and survival in vivo. Brain Res Brain Res Protoc 2001, 7: 255-60.
6. J.H. Weishaupt and M. Bähr. Degeneration of axotomized retinal ganglion cells as a model for neuronal apoptosis in the central nervous system - molecular death and survival pathways. Restor Neurol Neurosci 2001, 19: 19-27.

Book Chapters:

1. M. V. Catania, J.H. Weishaupt, T. Melcher, J. R. P. Geiger, P. Jonas und H. Monyer. Glutamate Receptor Subunit Composition in Principle Neurons and Interneurons of the CNS. S. 45-52. In "Excitatory Amino Acids and the Cerebral Cortex". (1996) F. Conti, T. P. Hicks, Herausgeber. The MIT Press, Cambridge, MA, USA.
2. K. Meuer, M. Bähr und J.H. Weishaupt. CDK5 and mitochondrial cell death pathways. L.-H. Tsai, Herausgeberin. (2007) Springer Science and Business Media, Norwell, MA, USA.

Patent:

1. H. Ehrenreich, R. Hardeland, K.-A. Nave, J.H. Weishaupt. Method of treating Amyotrophic Lateral Sclerosis Using Melatonin. 22.04.2008, United States Patent No. US 7,361,681 B2.

Sabine Ceremella

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Katrin Eckermann

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Tobias Frank, MD

phone:

+ 49 - 551 - 39 14139

fax:

+ 49 - 551 - 39 14302

e-mail:

tobias.frank(at)med.uni-goettingen.de

Main Research Interest

• Neuroprotective strategies in models of neurodegeneration
• Role of cytokines in neurodegenerative diseases
• MPTP-induced dopaminergic cell loss as a model for Parkinson Disease
• Clinical focus: neurodegenerative diseases (PD, ALS, movement disorders)

Curret Focus

Symptoms of Parkinson´s disease (PD) are caused by a slowly progressive degeneration of dopaminergic neurons in the substantia nigra. The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells.

Its function is mediated via the G-CSF receptor, which is expressed not only on haematopoietic cells but also by dopaminergic neurons of the substantia nigra (SN), suggesting that G-CSF might be neuroprotective for dopaminergic neurons and a candidate molecule for the treatment of PD.

Recently, our group provided proof-of-principle that daily G-CSF (Filgrastim) application significantly reduces dopaminergic cell death in in vitro and in vivo models of PD. Indicating preservation of dopaminergic terminals in the striatum, G-CSF alleviated striatal dopamine depletion after MPTP application in G-CSF-treated mice.

Pharmacologically modified forms of G-CSF with a longer half-life time (Pegfilgrastim) could improve patient compliance and acceptance of G-CSF as a neuroprotective therapy for PD.

Figure: Treatment of C57/BL mice with MPTP results in a selective loss of dopaminergic cells in the substantia nigra (B). Subcutaneous application of pegylated G-CSF protects from this toxicity in a dose dependent manner (C, diagram).

Bettina Goericke, MD

phone:

+ 49 - 551 - 39 14303

fax:

+ 49 - 551 - 39 14302

e-mail:

bgoericke(at)med.uni-goettingen.de

Christine Poser, TA

phone:

+ 49 - 551 - 39 14303

fax:

+ 49 - 551 - 39 14302

e-mail:

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