Miroslava Anděrová, PhD.
Phone: +420 241 062 050
Phone: +420 241 062 050
The Department of Cellular Neurophysiology is focused on the research of the morphological and electrophysiological properties of glial cells. We investigate their functions in the pathophysiology of central nervous system disorders, such as focal cerebral ischemia, amyotrophic lateral sclerosis, Alzheimer's disease, schizophrenia, and tumorigenesis. We focus primarily on astrocytes and polydendrocytes (also known as NG2 glia), and using genetically modified mouse strains and new technologies specifically designed for the research of glial cells, we study the role of ion and water channels in cerebral edema and post-ischemic regeneration. In addition, we investigate the role of Wnt signaling in neurogenesis and gliogenesis following ischemic brain injury, at the single-cell level.
Jana Turečková, PhD
Phone: +420 241 062 058
Miroslava Anděrová, PhD
Dr. Martina Chmelová, PhD
Assoc. prof. Daniel Jirák, PhD
Denisa Kirdajová, PhD
Ján Kriška, PhD
Jana Turečková, PhD
Lukáš Valihrach, PhD
Assoc. prof. Lýdia Vargová, MD, PhD
Tereza Filipi, MSc
Alice Foltýnová, MSc
Zuzana Heřmanová, MSc
Tomáš Knotek, MSc
Valeria Marchetti, MSc
Ondřej Vaňátko, MSc
Natalia Ziólkowska, MSc
Monika Kubísková, BSc
Markéta Hemerová, MSc
Natália Sirotová, MSc
We have shown here that APP Swedish, MAPT P301L, and PSEN1 M146V mutations in the murine model of Alzheimer’s disease lead to the structural changes in the extracellular space differing from those observed in physiological aging. We suggest that they are caused by cell atrophy on the one hand and shifts and changes in the ECS content including an increase of the diffusion obstacles (barriers) on the other.
Scheme describing the major changes in astrocyte channel/transporter expression and extracellular matrix structure resulting in the altered ability of astrocytes to uptake ions and neurotransmitters from the extracellular space (ECS) and regulate their cell volume. Schematic illustration of astrocyte morphological changes, extracellular matrix structure, and changes in astrocytic channel and transporter expression in Ctrl (A) and triple transgenic (3xTgAD) mouse models of Alzheimer's disease (B).
Collaboration: Institute of Biotechnology CAS
Tureckova, J.; Kamenicka, M.; Kolenicova, D.; Filipi, T.; Hermanova, Z.; Kriska, J.; Meszarosova, L.; Pukajova, B.; Valihrach, L.; Androvic, P.; Zucha, D.; Chmelova, M.; Vargova, L.; Anderova, M. Compromised Astrocyte Swelling/Volume Regulation in the Hippocampus of the Triple Transgenic Mouse Model of Alzheimer's Disease. Front Aging Neurosci. 2022 Jan 27;13:783120. doi: 10.3389/fnagi.2021.783120. eCollection 2021.
Wnt signaling influences the fate of stem cells in the adult brain. Its modulation can represent the treatment of a stroke, which we induced in laboratory mice by occlusion of the middle cerebral artery. Based on electrophysiological measurements and analyzes of gene and protein expression, we found that Wnt signaling promotes the proliferation of stem cells and their differentiation into neuronal precursors. Our observations suggest that Wnt signaling promotes neurogenesis and enhances brain regeneration after stroke.
According to our immunohistochemical analyses, Wnt signaling inhibition (dnTCF4 or Dkk1) led to the differentiation of neural stem/progenitor cells into astrocytes, while activation of the pathway (constitutively active β-catenin) promoted neurogenesis. A similar impact of Wnt signaling manipulation after ischemia was also confirmed by the patch-clamp technique. Larger cells represent a greater effect of Wnt signaling after ischemia. Abbreviations: Dkk1, Dickkopf 1; dnTCF4, dominant negative T-cell factor 4.
Collaboration: Institute of Molecular Genetics CAS
Kriska, J; Janeckova, L; Kirdajova, D; Honsa, P; Knotek, T; Dzamba, D; Kolenicova, D; Butenko, O; Vojtechova, M; Capek, M; Kozmik, Z; Taketo, MM; Korinek, V; Anderova, M. Wnt/β-Catenin Signaling Promotes Differentiation of Ischemia-Activated Adult Neural Stem/Progenitor Cells to Neuronal Precursors. Front Neurosci. 2021 Feb 25;15:628983. doi: 10.3389/fnins.2021.628983. eCollection 2021.
In the study, we demonstrated the broad proliferation and differentiation potential of NG2 glia (the fourth type of glial cells in the brain) under physiological and pathological conditions. To compare these properties, we used three types of brain disorders – focal cerebral ischemia, cortical stab wound, and demyelination. Our results demonstrated that a specific subpopulation of NG2 glia (astrocyte-like NG2 glia) appeared transiently only after focal brain ischemia. These cells, located in the post-ischemic glial scar, were active in the cell cycle and displayed a current profile similar to that identified in cortical astrocytes. Astrocyte-like NG2 glia may represent important players in the processes of glial scar formation and repair after ischemia.