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Neuron in action
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CNSR Central Nervous System Research

Loss of functional neuronal circuits is a hallmark of numerous central nervous system (CNS) pathologies, including traumatic brain injuries (TBI), stroke, neurodegenerative disorders, and brain cancers. The limited recovery of neuronal circuit functionality remains a major challenge in treating these conditions, leading to poor outcomes despite the availability of curative therapies.

In TBI, a regulated neuroinflammatory response activates glial cells (reactive gliosis) and recruits them to the injury site. This reactive gliosis is critical for wound healing; however, it also triggers permanent changes in the extracellular matrix, impeding the integration of new neurons—whether transplanted or generated in situ through direct reprogramming. Additionally, reactive glial cells contribute to secondary pathologies such as neurodegeneration, epilepsy, and glioblastomas. These adverse effects primarily arise from prolonged neuroinflammation at the injury site.

Interestingly, zebrafish possess efficient mechanisms to overcome these obstacles, enabling them to regenerate lost neurons and fully restore damaged neuronal circuits. Zebrafish initiate a neuroinflammatory response to brain injury similar to mammals, but crucially, they limit glial activity once wound healing is complete. This restriction prevents long-term changes that could interfere with recovery or promote pathologies such as glioblastoma (Baumgart et al., 2012; Sanchez et al., 2022; Zambusi et al., 2022; Di Giaimo et al., 2018).

Our translational, cross-species research aims to uncover the cellular and molecular mechanisms underlying zebrafish’s restorative neurogenesis and controlled glial responses. We seek to adapt these findings for mouse models of cerebral cortex injury and human brain organoids, ultimately laying the groundwork for regenerative therapies applicable to human brain diseases.

Loss of functional neuronal circuits is a hallmark of numerous central nervous system (CNS) pathologies, including traumatic brain injuries (TBI), stroke, neurodegenerative disorders, and brain cancers. The limited recovery of neuronal circuit functionality remains a major challenge in treating these conditions, leading to poor outcomes despite the availability of curative therapies.

In TBI, a regulated neuroinflammatory response activates glial cells (reactive gliosis) and recruits them to the injury site. This reactive gliosis is critical for wound healing; however, it also triggers permanent changes in the extracellular matrix, impeding the integration of new neurons—whether transplanted or generated in situ through direct reprogramming. Additionally, reactive glial cells contribute to secondary pathologies such as neurodegeneration, epilepsy, and glioblastomas. These adverse effects primarily arise from prolonged neuroinflammation at the injury site.

Interestingly, zebrafish possess efficient mechanisms to overcome these obstacles, enabling them to regenerate lost neurons and fully restore damaged neuronal circuits. Zebrafish initiate a neuroinflammatory response to brain injury similar to mammals, but crucially, they limit glial activity once wound healing is complete. This restriction prevents long-term changes that could interfere with recovery or promote pathologies such as glioblastoma (Baumgart et al., 2012; Sanchez et al., 2022; Zambusi et al., 2022; Di Giaimo et al., 2018).

Our translational, cross-species research aims to uncover the cellular and molecular mechanisms underlying zebrafish’s restorative neurogenesis and controlled glial responses. We seek to adapt these findings for mouse models of cerebral cortex injury and human brain organoids, ultimately laying the groundwork for regenerative therapies applicable to human brain diseases.

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About our Research

About our Research

Our research focuses on three key challenges in regenerative medicine:


A) Generating new neurons to repair non-functional circuits.
B) Minimizing secondary tissue damage caused by scar formation.
C) Restricting the impact of the glial scar on cellular changes that lead to psychiatric disorders or cancers.

Nervenzelle in Aktion
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2022 Wissenschaftlicher Artikel in Nature Neuroscience Nat. Neurosci. 25, 1608-1625 (2022)

Zambusi, A. ; Novoselc, K.T. ; Hutten, S. ; Kalpazidou, S. ; Koupourtidou, C. ; Schieweck, R. ; Aschenbroich, S. ; Silva, L. ; Yazgili, A.S. ; van Bebber, F. ; Schmid, B. ; Möller, G. ; Tritscher, C. ; Stigloher, C. ; Delbridge, C. ; Sirko, S. ; Günes, Z.I. ; Liebscher, S. ; Schlegel, J. ; Aliee, H. ; Theis, F.J. ; Meiners, S. ; Kiebler, M. ; Dormann, D. ; Ninkovic, J.

TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury.

2022 Wissenschaftlicher Artikel in Cells Cells 11:520 (2022)

Sanchez-Gonzalez, R. ; Koupourtidou; C. ; Lepko, T. ; Zambusi, A. ; Novoselc, K.T. ; Durovic, T. ; Aschenbroich, S. ; Schwarz, V. ; Breunig, C. ; Straka, H. ; Huttner, H.B. ; Irmler, M. ; Beckers, J. ; Wurst, W. ; Zwergal, A. ; Schauer, T. ; Straub, T. ; Czopka, T. ; Trümbach, D. ; Götz, M. ; Stricker, S.H. ; Ninkovic, J.

Innate immune pathways promote oligodendrocyte progenitor cell recruitment to the injury site in adult Zebrafish brain.

2022 Wissenschaftlicher Artikel in EMBO Molecular Medicine EMBO Mol. Med.:e14797 (2022)

Giehrl-Schwab, J. ; Giesert, F. ; Rauser, B. ; Lao, C.L. ; Hembach, S. ; Lefort, S. ; Ibarra Del Rio, I.A. ; Koupourtidou; C. ; Luecken, M. ; Truong, D.-J.J. ; Fischer-Sternjak, J. ; Masserdotti, G. ; Prakash, N. ; Ninkovic, J. ; Hölter, S.M. ; Vogt Weisenhorn, D.M. ; Theis, F.J. ; Götz, M. ; Wurst, W.

Parkinson's disease motor symptoms rescue by CRISPRa-reprogramming astrocytes into GABAergic neurons.

2019 Wissenschaftlicher Artikel in EMBO Journal, The EMBO J. 38:e100481 (2019)

Lepko, T. ; Pusch, M. ; Müller, T. ; Schulte, D. ; Ehses, J. ; Kiebler, M. ; Hasler, J. ; Huttner, H.B. ; Vandenbroucke, R.E. ; Vandendriessche, C. ; Modic, M. ; Martin-Villalba, A. ; Zhao, S. ; LLorens-Bobadilla, E. ; Schneider, A. ; Fischer, A. ; Breunig, C. ; Stricker, S.H. ; Götz, M. ; Ninkovic, J.

Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain.

2016 Wissenschaftlicher Artikel in Cell Cell 166, 867-880 (2016)

García-Cáceres, C. ; Quarta, C. ; Varela, L. ; Gao, Y. ; Gruber, T. ; Legutko, B. ; Jastroch, M. ; Johansson, P.A. ; Ninkovic, J. ; Yi, C.-X. ; Le Thuc, O. ; Szigeti-Buck, K. ; Cai, W. ; Meyer, C.W. ; Pfluger, P.T. ; Fernandez, A.M. ; Luquet, S. ; Woods, S.C. ; Torres-Alemán, I. ; Kahn, C.R. ; Götz, M. ; Horvath, T.L. ; Tschöp, M.H.

Astrocytic insulin signaling couples brain glucose uptake with nutrient availability.

2013 Wissenschaftlicher Artikel in Cell Stem Cell Cell Stem Cell 13, 403-418 (2013)

Ninkovic, J. ; Steiner-Mezzadri, A. ; Jawerka, M. ; Akinci, U. ; Masserdotti, G. ; Petricca, S. ; Fischer, J. ; von Holst, A. ; Beckers, J. ; Lie, D.C. ; Petrik, D. ; Miller, E. ; Tang, J. ; Wu, J. ; Lefebvre, V. ; Demmers, J. ; Eisch, A. ; Metzger, D. ; Crabtree, G. ; Irmler, M. ; Poot, R. ; Götz, M.

The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network.