Research Group Experimental Deep brain Stimulation

The research group Experimental Deep Brain Stimulation (head: Dr. med. Mareike Fauser) is primarily interested in understanding the effects and mechanisms of action of deep brain stimulation in a model of Parkinson's disease. Our goal is to better characterize this treatment method, which has been available in clinical application for decades, and thus to contribute to an optimization of deep brain stimulation in Parkinson's patients in the future.

Parkinson's disease is one of the most common neurodegenerative diseases with a prevalence of about 100 per 100,000 in the age group up to 60 years, which, however, already rises to about 3,000 per 100,000 among those over 80. The clinical presentation is classically with a triad of (resting) tremor , rigidity and bradykinesia. In recent years and decades, however, it has become increasingly apparent that so-called non-motor symptoms also play a significant role, especially concerning patients' quality of life. Certain non-motor symptoms (e.g., olfactory disorders and REM sleep behaviour disorders) can even occur before the onset of motor symptoms. Up to now, available treatment options have been exclusively symptomatic in nature; disease modification is still out of reach. To date, deep brain stimulation (DBS) in Parkinson's disease patients is mainly used in the middle and late stages of the disease, when drug therapy approaches no longer lead to sufficient symptom relief, though DBS could have the potential to also alleviate early-onset non-motor symptoms.

In our research group we are currently investigating the effect of DBS on cellular plasticity in different dopaminergic systems as well as on adult neurogenesis in an established hemiparkinsonian model. We are particularly interested in the potential relationships between cellular plasticity and non-motor symptoms of Parkinson's disease. Furthermore, we work on the influences of DBS on the expression of trophic factors in certain brain areas. These data are additionally verified by in vitro studies on neural stem cells.

Within the Collaborative Research Center "ELAINE - Electrically Active Implants" we are working on the technical optimization of preclinical stimulation systems (subproject C04; funded by the German Research Society III/2017-II/2021), in order to be able to work with fully implantable stimulation systems in experimental models (in cooperation with the Institute of Applied Microelectronics and Data Technology, Prof. Dirk Timmermann). With these, functional influences can be investigated much better than with external stimulators available so far. In addition, we are investigating the field distribution as well as potential influences of  electrode materials and the stimulation modes on the effects of DBS  with colleagues from electrical engineering (Institute of General Electrical Engineering, Chair of Theoretical Electrical Engineering, Prof. Ursula van Rienen) within the CRC.

Group Leader

Dr. med. Mareike Fauser

 

Equipment (a selection):

  • Digital two-arm stereotaxic frame (Stoelting Neuroscience)

  • Research Cryostat /Cryomicrotome CM3050S  (Leica)*

  •  High-resolution fluorescence microscope AxioObserver.Z1 with Apotome (Zeiss)

    * co-financed by the European Union from the European Regional Development Fund

Publications

  1. Fauser M, Weselek G, Hauptmann C, Markert F, Gerlach M, Hermann A, Storch A.  „Catecholaminergic innervation of periventricular neurogenic regions of the developing mouse brain”. In: Front Neuroanat 14 (2020).
  2. Weselek G, Keiner S, Fauser M, Wagenführ L, Müller J, Kaltschmidt B, Brandt MD, Gerlach M, Redecker C, Hermann A, and Storch A. “Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche”. In: Stem Cells 38.9 (2020), pp. 1188–201.
  3. Schneider CB, Donix M, Linse K, Werner A, Fauser M, Klingelhoefer L, Löhle M, von Kummer R, Reichmann H; LANDSCAPE consortium, Storch A. “Am J Alzheimers Dis Other Demen. 32.6 (2017), pp. 313-319.
  4. Ossig C, Sippel D, Fauser M, Gandor F, Jost WH, Ebersbach G, Storch A. Timing and Kinetics of Nonmotor Fluctuations in Advanced Parkinson's Disease. In: J Parkinsons Dis. 7.2 (2017), pp. 325-330.
  5. Thurm F, Schuck NW, Fauser M, Doeller CF, Stankevich Y, Evens R, Riedel O,Storch A, Lueken U, and Li SC. “Dopamine modulation of spatial navigation memory in Parkinson’s disease”. In: Neurobiol Aging 38 (2016), pp. 93–103.
  6. Fauser M, Löhle M, Ebersbach G, Odin P, Fuchs G, Jost WH, Chaudhuri KR, Koch R, NoMoFlu-PD study group, and StorchA. “Intraindividual Variability of Nonmotor Fluctuations in Advanced Parkinson’s Disease”. In:J Parkinsons Dis 5.4 (2015),pp. 737–741.
  7. Müller J, Ossig C, Greiner JF, Hauser S, Fauser M, Widera D, Kaltschmidt C, Storch A, and Kaltschmidt B. “Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats”. In: Stem Cells Transl Med 4.1 (2015), pp. 31–43.
  8. Wolz M, Hauschild J, Koy J, Fauser M, Klingelhöfer L, Schackert G, Reichmann H, and Storch A. “Immediate effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms in Parkinson’s disease”. In: Parkinsonism Relat Disord 18.8 (2012), pp. 994–997.
  9. Hermann A, Suess C, Fauser M, Kanzler S, Witt M, Fabel K, Schwarz J, Höglinger GU, and Storch A. “Rostro-caudal gradual loss of cellular diversity within the periventricular regions of the ventricular system”. In: Stem Cells 27.4 (2009), pp. 928–941.

Dopaminergic plasticity

Figure 1: Influence of deep brain stimulation in the subthalamic nucleus (STN) or SHAM stimulation on the number of dopaminergic (dopamine producing) neurons in the midbrain in a hemiparkinson model (immunohistochemical staining of tyrosine hydroxylase using DAB) on the lesioned and non-lesioned hemisphere (a, b) in the substantia nigra pars compacta (SNpc; c, d) and the ventral tegmental area (VTA; e, f).

 

Neurogenesis in the olfactory bulb:

Figure 2: Influence of deep brain stimulation in the subthalamic nucleus (STN) and internal globus pallidus pars (GPI) or SHAM stimulation on neurogenesis in the granular zone of the olfactory bulb, demonstrated by incorporation of thymidine analogues, whichhad been administered at different time points after stimulation onset (IdU = iododeoxyuridine; CldU = chlorodeoxyuridine). Cell nuclei were labelled with 4′,6-diamidine-2-phenylindole (DAPI, blue).

 

Present Members:

Dr. med. Mareike Fauser, junior group leader

Dipl. Biol. Francia Molina, research associate

Uta Naumann, veterinary engineer

M.Sc. Maria Kober, PhD student

M.Sc. Jennifer Käthner, PhD student

B. Sc. Nikolai Weis, master student

Franziska Backhaus, MD student

Felix Bernsdorff, MD student

Charlotte Helf, MD student

Martin Nüssel, MD student

Leonie Overhoff, MD student

Maximilian Steinigk, MD student

 

Past members:

Dr. rer. nat. Kathrin Badstübner-Meeske

Dr. med. Manuel Ricken