Researchgate: https://www.researchgate.net/profile/Anja-Urbach
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 in 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). Accordingly, recent evidence suggests that adult neurogenesis plays important roles in memory and mood regulation, and perturbations of this process have been linked to neurological diseases and cognitive aging.
The source of lifelong neurogenesis lies in a small population of radial glia-like neural stem cells that is established during early postnatal development and declines with increasing age. We aim to understand from where these cells originate, the origin and the extent of their heterogeneity, and how and why they age.
D-type cyclins are a family of proteins essential for cell cycle progression from G1- to S-phase. Among them, cyclin D2 appears to be 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 aimed to identify the role of D-type cyclins for the proliferation, fate determination and differentiation of adult stem and progenitor cells. We also investigate their role during development of the dentate gyrus and in particular for the formation of the adult stem cell pool.
Whether and how adult-born neurons contribute to brain function is a central question in the field of adult neurogenesis. Our current projects aim to characterize the contribution of newborn neurons to hippocampal function and to experience-dependent plasticity, both in the adult and in the aged brain.
Cortical spreading depolarizations (CSD) have been discovered some 70 years ago by the Brazilian physiologist Aristides P. Leao. Since then they have been identified in various species including rodents and primates. CSD are characterized by a wave of neuronal and glial depolarization that slowly propagates from a trigger point across the ipsilateral grey matter. They are associated with a transient depression of neuronal activity, as well as pronounced imbalances in ionic, metabolic and hemodynamic parameters. In recent years CSD have been demonstrated also in the human brain where they occur spontaneously in different neuropathologies (ischemic stroke, hemorrhage, traumatic brain injury and migraine). While CSD are completely reversible and benign in normoxic tissue, they lead to secondary expansion of the necrotic territory in the injured brain. In our projects we explore the potential duality (detrimental and beneficial) in how CSD contribute to the outcome of associated neuropathologies, focussing on their effects on reorganization and plasticity in healthy and remote perilesional brain areas.
Pensold D, Reichard J, Van Loo KMJ, Ciganok N, Hahn A, Bayer C, Liebmann L, Groß J, Tittelmeier J, Lingner T, Salinas-Riester G, Symmank J, Halfmann C, González-Bermúdez L, Urbach A, Gehrmann J, Costa I, Pieler T, Hübner CA, Vatter H, Kampa B, Becker AJ, Zimmer-Bensch G: DNA Methylation-Mediated Modulation of Endocytosis as Potential Mechanism for Synaptic Function Regulation in Murine Inhibitory Cortical Interneurons. Cerebral Cortex, 2020; https://doi.org/10.1093/cercor/bhaa009
Trautmann C, Bock A, Urbach A, Hübner CA, Engmann O: Acute vitamin B12 supplementation evokes antidepressant response and alters Ntrk-2. Neuropharmacology, 2020. https://doi.org/10.1016/j.neuropharm.2020.108112
Hahn A, Bayer C, Pensold D, Tittelmeier J, Marx-Bluemel L, Gonzalez-Bermudez L, Linde J, Gross J, Salinas-Riester G, von Maltzahn J, Spehr M, Pieler T, Urbach A, Zimmer-Bensch G: DNA methyltransferase 1 (DNMT1) function is implicated in the age-related loss of cortical interneurons. Front Cell Dev Biol, 2020; https://doi.org/10.3389/fcell.2020.00639
Grünewald G, Wickel J, Hahn N, Hörhold F, Rupp H, Chung HY, Haselmann H, Strauss AS, Schmidl L, Hempel N, Grünewald L, Urbach A, Bauer M, Toyka KV, Blaess M, Claus RA, König R, Geis C: Targeted rescue of synaptic plasticity improves cognitive decline after severe systemic inflammation. bioRxiv 2021. https://doi.org/10.1101/2021.03.04.433352
IZKF Advanced Medical Scientist program, 2019-2022
New Bachelor or Master students are always welcome. We are currently seeking for highly motivated students to support our research on the developing and aging stem cell niche.
