Department of Neurology

Hippocampal Plasticity and neurogenesis

Principal Investigator

Anja Urbach, PhD

Postdoc
Research Group Leader


Phone: 03641-9 32 35 38
Website
 

Group members

Alumni

Dr. med. Judith Brückner

Dr. med. Urike Rüddel (IZKF-funded)

Dr. med. Hannah Zipprich (IZKF-funded)

Dipl. Biol. Eileen Baum (LGSA-funded)

B.Sc. Marcel Brosch

B.Sc. Sissy Schaller

M.Sc. Katja Bornkessel

Dipl. Biol. Lena Schumacher

Dipl. Biol. Anne Ansorg

M.Sc. Jaya Keertana Srimat Kandadai

B.Sc. Felix Tetzlaff

B.Sc. Ronja Badelt

M.Sc. Vanessa Knölker

B.Sc. Bente Kaske

B.Sc. Enno Bockelmann

 

Previous and current research

1. Functional role of adult neurogenesis

It was in the 1960´s when the first evidence emerged against Cajal´s dogma that new neurons cannot be produced in the adult brain. Since then it became widely accepted that new neurons are generated continuously in two regions of the mammalian brain: the olfactory bulb and the dentate gyrus of the hippocampus. In the dentate gyrus, adult-born neurons are derived from neural progenitors and go through different stages of morphological and physiological development before reaching maturity, a process that takes several weeks and is influenced by an animal´s experience. During a critical period of their development immature neurons provide the local circuitry with unique functional properties (high excitability, enhanced synaptic plasticity). Whether and how this unique form of cellular and physiological plasticity contributes to brain function is a central question in the field of neurogenesis. Our current projects aim to characterize the contribution of newborn neurons to hippocampal function and experience-dependent plasticity, both in the adult and aged brain.

Anja

2. Role of D-type cyclins in adult neural stem and progenitor cells

D-type cyclins are a family of proteins essential for cell cycle progression from G1- to S-phase. Among them, cyclin D2 is of particular importance for adult neurogenesis. We have shown that ablation of the gene coding for cyclin D2 in mice leads to virtual absence of newborn dentate granule neurons from adolescence on. Our ongoing work is intended to identify the role of D-type cyclins for the proliferation, fate determination and differentiation of adult neural stem and progenitor cells.   

3. Morphogenesis of the dentate gyrus and development of the adult stem cell niche

In this project we investigate thr role of D-cyclins for the development of the adult neurogenic niche in the dentate gyrus.

4. Cortical spreading depression

Cortical spreading depression (CSD) was discovered almost 70 years ago by the Brazilian physiologist Aristides P. Leao. Since then it has been identified in various species including rodents and primates. CSD is characterized by a wave of neuronal and glial depolarization that slowly propagates from a trigger point across the ipsilateral grey matter. It is associated with a transient depression of neuronal activity, as well as pronounced imbalances in ionic, metabolic and hemodynamic parameters. In recent years CSD has been unequivocally demonstrated also in the human brain where it is involved in different neuropathologies (ischemia, hemorrhage, traumatic brain injury and migraine). While CSD is completely reversible and benign in the normoxic tissue, it leads to secondary expansion of the necrotic territory in the ischemic brain. In our projects we explore how CSD contributes to the pathophysiology of the associated neuropathologies as well as to reorganization and plasticity in the healthy perilesional brain parenchyma following stroke.

 

Methods

  • Rodent behavior (Morris water maze, Barnes Maze, Fear conditioning, Open field, Object/Location novelty recognition, Novelty suppressed feeding, Tail suspension Test, RotaRod, Grid walk)
  • Rodent stroke models (MCAO, photothrombosis)
  • Immunohistochemistry, confocal laser scanning microscopy (LSM), stereology
  • Molecular biology (RNA, DNA, qRT-PCR, microarray, cloning)
  • Generation of knock-out mice
  • Electrophysiology (extracellular field potentials, EEG and direct current potential in vivo)
  • 14C-2-deoxyglucose mapping of cortical representations after sensory deprivation  (in cooperation with RG Neuroplasticity, Nencki Institute Warsaw)

 Publications

  • Urbach A, Bruehl C, Witte OW: Microarray based long term detection of genes differentially expressed after cortical spreading depression. Eur J Neurosci, 24(3), 2006
  • Urbach A, Redecker C, Witte OW: Induction of neurogenesis in the adult dentate gyrus by cortical spreading depression. Stroke 39(11), 2008
  • Popp A, Urbach A, Witte OW, Frahm C: Adult and juvenile GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain. PlosONE 4(2), 2009
  • Ansorg A, Witte OW, Urbach A: Age-dependent kinetics of dentate gyrus neurogenesis in the absence of cyclin D2. BMC Neuroscience 13, 2012.
  • Urbach A, Robakiewicz I, Baum E, Kaczmarek L, Witte OW, Filipkowski RK: Cyclin D2 knockout mice with depleted adult neurogenesis learn Barnes maze task. Behav Neurosci 127(1), 2012
  • Schumacher L, Urbach A, Lutzenburg M, Bidmon HJ,Witte OW: Bihemispheric ischemic tolerance induced by unilateral focal cortical lesion. Brain Res 1570, 2014
  • Urbach A, Brueckner J, Witte OW: Cortical spreading depolarization stimulates gliogenesis in the rat entorhinal cortex. JCBFM, doi:10.1038/jcbfm.2014.232, 2014
  • Ansorg A, Bornkessel K, Witte OW, Urbach A: Immunohistochemistry and multiple labeling with antibodies from the same host species to study adult hippocampal neurogenesis. JoVE, doi: 10.3791/52551, 2015
  • Urbach A, Baum E, Braun F, Witte OW: Cortical Spreading Depolarization Increases Adult Neurogenesis, and Alters Behavior and Hippocampus-Dependent Memory in Mice. JCBFM, 2016; DOI: 10.1177/0271678X16643736
  • Hartings JA, Shuttleworth CW, Kirov SA, Ayata C, Hinzman JM, Foreman B, Andrew D, Boutelle MG, Brennan KC, Carlson AP, Dahlem MA, Drenckhahn C, Dohmen C, Fabricius M, Farkas E, Feuerstein D, Graf R, Helbok R, Lauritzen M, Major S, Oliveira-Ferreira AI, Richter F, Rosenthal ES, Sakowitz OW, Sánchez-Porras R, Santos E, Schöll M, Strong AJ, Urbach A, Westover MB, Winkler MKL, Witte OW, Woitzik J, Dreier JP: The continuum of spreading depolarizations in acute cortical lesion development: examining Leão’s legacy. JCBFM, 2016; DOI:10.1177/0271678X16654495

Funding

  • LGSA “Funktionelle Relevanz adulter hippocampaler Neurogenese nach kortikaler Spreading Depression”, 2006-2010
  • IZKF (J15) “Relevance of adult neurogenesis for the structural and functional plasticity of the hippocampus”, 2008-2010
  • Programm zur Förderung der Drittmittelfähigkeit von NachwuchswissenschaftlerInnen "Herstellung einer Cyclin D2fl/fl Mausstammzellinie als Voraussetzung zur Erzeugung einer konditionalen Cyclin D2-knock out Maus", 2010-2011
  • GRK1715, Project “Protective and Deleterious Consequences of Ischemic Preconditioning: The Janus Face of Adaptive Stress Responses”, 2011-2014
  • Prochance, 2016
  • DAAD, 2017

Open Positions, Master- and Bachelorprojects

New Bachelor or Master students are always welcome. We are currently seeking for highly motivated students to support our research on experience-induced hippocampal plasticity and on the role of cyclin D2 in hippocampal neurogenesis.