Moritz Brandt

Adult neurogenesis in a genetic mouse model of Parkinsons disease

The generation of new neurons in the adult dentate gyrus has functional implications for the hippocampal formation. Reduced hippocampal neurogenesis has been described in different animal models of hippocampal dysfunction like dementia or depression. Dementia and depression are common non-motor-symptoms of Parkinsons disease (PD). As dopamine (DA) plays an important role in regulating precursor cell proliferation, the loss of dopaminergic neurons in the substantia nigra (SN) in PD has been brought into connection with reduced neurogenesis in the neurogenic regions of the adult brain: subventricular zone (SVZ) and dentate gyrus (DG). We are examining adult hippocampal neurogenesis in Pitx3-mutant-mice, which phenotypically show an selective degeneration of DA neurons of the SN, while the ventral tegmental area (VTA) is unaffected in young animals and partial degenerates during adulthood. This genetic PD-animal-model gives us the opportunity to differentially investigate the influence of the SN and VTA on adult neurogenesis.

 

Hypoxia related signaling in adult hippocampal precursor cells

Oxygen-related gene expression is reported crucial for affecting stem and progenitor cell behavior with hypoxia-inducible factor-1a (HIF-1α) as one major oxygen-sensing molecule regulating several genes involved in neurogenesis, such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO). Another important oxygen-sensitive signaling pathway is the intracellular Notch1 pathway. Notch has multiple function during all steps of neuronal development: e.g. stem-cell maintenance, inhibition of neuronal differentiation, survival and dendritic maturation of postmitotic neurons. The aim of our project is to investigate the role of Notch1, VEGF and other hypoxia-inducible factors in adult hippocampal neurogenesis. We are using voluntary exercise (wheel running) as a well-established physiological stimulator of adult neurogenesis to investigate the expression of hypoxia related genes and growth-factors in vivo. Furthermore, we take advantage of two knock-out models that lack the expression of VEGF-receptor type 2 (flk1) and Hif-1a respectively in neural progenitor cells.
 
 
Cell cycle kinetics in adult hippocampal neurogenesis

Stem and precursor cells of the adult hippocampus show differences in mitotic frequency and length of cell cycle phases. Depending on the developmental stage they divide symmetrically or asymmetrically. Thus the pool of proliferating cells in the subgranular zone of the hippocampus is very heterogeneous regarding mitotic activity and the production of progenies. Our aim is to investigate the cell specific cell cycle characteristics of different precursor populations.
 





 
The relation of sleep and cellular plasticity in the hippocampus
 

Translationale Forschung (HICH-Studie)

 


 
Curriculum Vitae                            Dr. med. Moritz Brandt
 
 
Personal
 
 
Name:                         Moritz Daniel Brandt
Date of birth:               October 17th, 1977
Place of birth:              Essen, Germany
Email:                            Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein!
 



Education
 
 
 
1998-2006             Medical student at the University of Leipzig and Humboldt-University Berlin (Charité)
2001-2003             Thesis at the Max-Delbrück-Center for Molecular Medicine, Berlin.
Research group “Neuronal Stem Cells” (Prof. Dr. Gerd Kempermann)
07/2006                 State examination (Staatsexamen) and doctoral degree
Thesis title: Adulte Neurogenese im murinen Hippocampus: Phasenspezifische Calretininexpression in unreifen Neuronen.
Since 11/2006        Resident (Arzt in Weiterbildung) at the Department of Neurology, Carl Gustav Carus Universitätsklinikum Dresden.
                            Clinicalfocus:Neurological sleep disorders
                            Postdoc research group “Neuroregeneration” (Prof. Dr. A. Storch)

 

Publications
 
 
Brandt MD, Maass A, Kempermann G, Storch A.
Physical exercise increases Notch activity, proliferation and cell cycle exit of type-3 progenitor cells in adult hippocampal neurogenesis..
Eur J Neurosci. 2010 Oct; 32(8):1256-64
 
Hermann A, Brandt MD, Loewenbrueck KF, Storch A.
“Silenced” polydendrocytes: A new cell type within the oligodendrocyte progenitor cell population?
Cell Tissue Res. 2010 Apr; 340(1): 45-50. Review
                                                          
Brandt MD, Storch A.
Neurogenesis in the adult brain: from bench to bedside?.
Fortschr Neurol Psychiatr. 2008 Sep; 76(9):517-29. Review
 
Plümpe T, Ehninger D, Steiner B, Jessberger S, Klempin F, Brandt MD, Römer B, Rodriguez GR, and Kempermann G.
Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation.
BMC Neurosci. 2006 Nov 15;7:77.
 
Steiner B, Kronenberg G, Jessberger S, Brandt MD, Reuter K, Kempermann G.
Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice.
Glia. 2004 Apr 1;46(1):41-52.
 
Kronenberg G, Reuter K, Steiner B, Brandt MD, Jessberger S, Yamaguchi M, Kempermann G.
Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli.
J Comp Neurol. 2003 Dec 22;467(4):455-63.
 
Brandt MD, Jessberger S, Steiner B, Kronenberg G, Reuter K, Bick-Sander A, von der Behrens W, Kempermann G.
Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice.

Mol Cell Neurosci. 2003 Nov;24(3):603-13.