Project 2 [ended]

Mechanisms of nigral neuroprotection and striatal neuroplasticity following Deep brain stimulation of the subthalamic nucleus

Projekt description:

Parkinson’s disease (PD) is a neurodegenerative disorder that affects around 6 million people worldwide. The main pathology of the disease is a chronic progressive loss of dopaminergic neurons of the substantia nigra pars compacta that leads to an impairment of information processing within the basal ganglia loop. The subsequent pathologic network activity ultimately results in the characteristic symptoms of the patients. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for patients with advanced stages of PD. Although STN-DBS is applied to patients worldwide, its mechanism of action is still incompletely understood.

Local field potentials from the Cortex and STN of native and 6-OHDA lesioned animals

The main focus of our group is to elucidate the functional principle of deep brain stimulation using animal models of PD (6-OHDA and MPTP). Using a fully implantable DBS-system for rodents, developed by our group, we investigate how chronic DBS influences the brain´s structure (light & electron microscopy), neurochemistry (HPLC, western blot, ELISA) and information processing (in vivo electrophysiology of freely moving subjects). Focussing especially on the spatiotemporal dynamics of PD, we hope to contribute to the development of improved DBS paradigms to reduce the disease burden of patients.

DBS System for rats


Dr. med. Daniel Harnack, Projektleiter
Charité – Campus Virchow Klinikum
Department of Neurology / AG Bewegungsstörungen
Augustenburger Platz 1
13353 Berlin
Tel.: +49-30-450 525 194
Fax: +49-30-450 525 919
E-mail: daniel.harnack@charite.de
Prof. Dr. med. Andreas Kupsch, Projektleiter
E-mail: andreas.kupsch@charite.de
Dr. med. Christoph Gertler, Postdoc
Charité – Campus Virchow Klinikum
Department of Neurology / AG Bewegungsstörungen
Augustenburger Platz 1
13353 Berlin
Tel.: +49-30-450 525 194
Fax: +49-30-450 525 919
E-mail: christoph.gertler@charite.de
Jens-Kersten Haumesser, PhD Student
E-Mail: jens-kersten.haumesser@charite.de
Simon Hellwig, PhD Student
E-Mail: simon.hellwig@charite.de
Nele Elisa Bubel, PhD Student
E-Mail: nele-elisa.bubel@charite.de

Selected Publications:

Placebo-controlled chronic high-frequency stimulation of the subthalamic nucleus preserves dopaminergic nigral neurons in a rat model of progressive Parkinsonism. Harnack D, Meissner W, Jira JA, Winter C, Morgenstern R, Kupsch A. Exp Neurol. 2008 Mar;210(1):257-60. Epub 2007 Oct 22.

Continuous high-frequency stimulation in freely moving rats: development of an implantable microstimulation system. Harnack D, Meissner W, Paulat R, Hilgenfeld H, Müller WD, Winter C, Morgenstern R, Kupsch A. J Neurosci Methods. 2008 Jan 30;167(2):278-91. Epub 2007 Aug 31.

Increased slow oscillatory activity in substantia nigra pars reticulata triggers abnormal involuntary movements in the 6-OHDA-lesioned rat in the presence of excessive extracellular striatal dopamine. Meissner W, Ravenscroft P, Reese R, Harnack D, Morgenstern R, Kupsch A, Klitgaard H, Bioulac B, Gross CE, Bezard E, Boraud T. Neurobiol Dis. 2006 Jun;22(3):586-98. Epub 2006 Mar 10.

Coherent spike-wave oscillations in the cortex and subthalamic nucleus of the freely moving rat. Magill PJ, Sharott A, Harnack D, Kupsch A, Meissner W, Brown P. Neuroscience. 2005;132(3):659-64.

Dopamine depletion increases the power and coherence of beta-oscillations in the cerebral cortex and subthalamic nucleus of the awake rat. Sharott A, Magill PJ, Harnack D, Kupsch A, Meissner W, Brown P Eur J Neurosci. 2005 Mar;21(5):1413-22.

Ablation of the subthalamic nucleus protects dopaminergic phenotype but not cell survival in a rat model of Parkinson’s disease. Paul G, Meissner W, Rein S, Harnack D, Winter C, Hosmann K, Morgenstern R, Kupsch A. Exp Neurol. 2004 Feb;185(2):272-80.