Mechanisms of Induced Plasticity of the Brain
Previous and Current Research
Our goal is to learn from zebrafish how to enable the adult brain to better cope with neurodegenerative disease and regenerate. The main motivation of our research group is to understand the molecular programs for zebrafish brain to induce regenerative stem cell plasticity. The brains of aging humans are prone to neurodegenerative disorders and we are unable to counteract neuronal loss by regenerating lost cells. Patients with neurodegenerative conditions progressively loose neurons yet cannot form new neurons that would replace the lost ones – namely, we humans lack the proper “plasticity response”. We are using zebrafish as a model organism that can regenerate its brain effectively. We try to learn from fish the molecular programs underlying such an aptitude, and developing innovative tools for comparative studies in mammalian brains.
Future Projects and Goals
We use zebrafish, 3D human brain cultures and mouse models of Alzheimer’s disease to investigate:
- The molecular mechanisms of neural stem cell plasticity and neurogenesis,
- Comparative aspects of AD pathology in zebrafish, humans and mouse
- The effects of neuroinflammation (e.g.: Interleukin-4) on neural stem cell proliferation and neurgenesis
Methodological and Technical Expertise
Our main goals are
- To identify the molecular mechanisms of neural stem cell plasticity and neurogenic ability in adult zebrafish brain
- To learn from zebrafish how to enable the adult brains to better cope with neurodegenerative disease and regenerate
- To translate the findings from zebrafish to mammalian models of Alzheimer's disease in 3D hydrogels and mouse
Kizil C, Bhattarai P
Is Alzheimer’s Also a Stem Cell Disease? – The Zebrafish Perspective.
Front Cell Dev Biol. 6:159 (2018)
Papadimitriou C, Celikkaya H, Cosacak MI, Mashkaryan V, Bray L, Bhattarai P, Brandt K, Hollak H, Chen X, He S, Antos CL, Lin W, Thomas AK, Dahl A, Kurth T, Friedrichs J, Zhang Y, Freudenberg U, Werner C, Kizil C
3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues Aβ42-Induced Loss of Human Neural Stem Cell Plasticity.
Developmental Cell. 46(1):85–101.e8 (2018)
Cosacak MI, Bhattarai P, Bocova L, Dzewas T, Mashkaryan V, Papadimitriou C, Brandt K, Hollak H, Antos CL, Kizil C
Human TAU(P301L) overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain.
Scientific Reports. 7(1):12959 (2017)
Bhattarai P, Thomas AK, Cosacak MI, Papadimitriou C, Mashkaryan V, Froc C, Reinhardt S, Kurth T, Dahl A, Zhang Y, Kizil C
IL4/STAT6 Signaling Activates Neural Stem Cell Proliferation and Neurogenesis upon Amyloid-β42 Aggregation in Adult Zebrafish Brain.
Cell Reports. 17(4):941–948 (2016)
Kyritsis N, Kizil C, Zocher S, Kroehne V, Kaslin J, Freudenreich D, Iltzsche A, Brand M
Acute inflammation initiates the regenerative response in the adult zebrafish brain.
Science. 338(6112):1353–6 (2012)