Nucleotide receptors govern proliferation and differentiation of human neural stem cells

• Antragsteller: Professor Dr. Herbert Zimmermann
• Fachliche Zuordnung: Klinische Neurologie; Neurochirurgie und Neuroradiologie
• Förderung: Förderung von 2007 bis 2010
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 22935240

• Erstellungsjahr: 2015

Zusammenfassung der Projektergebnisse

The study aimed at providing cues for improving the in vitro production of neurons, in particular of neurons with a dopaminergic phenotype. It was the goal of the project to analyse the functional expression of nucleotide receptors and their mechanistic role in affecting neural stem cell proliferation and differentiation in both human and mouse fetal neural stem cells. The project had proposed comparative and complementary approaches by using in parallel human (Leipzig) and mouse (Frankfurt) fetal neural progenitors. As a result of the reviewing process the human project (Leipzig) was excluded. Therefore the investigations were performed on mouse cells and in Frankfurt only. The data provide clear evidence that fetal mouse midbrain-derived neural precursors express a multitude of purinergic receptors and respond to a broad range of nucleotide receptor agonists. Nucleotides can be employed to enhance in vitro survival of young neurons and to increase the contribution of dopaminergic neurons to the total of precursor-derived neurons. Extracellular nucleotides can also negatively affect the survival of neurons in vitro. Our results demonstrate that nucleotides can be applied to enhance the formation of dopaminergic neurons from fetal mouse midbrain-derived neural precursors.

Projektbezogene Publikationen (Auswahl)

• Activationdependent trafficking of NTPDase2 in Chinese hamster ovary cells. Int J Biochem Cell Biol. 2007; 39: 810–7
  Vlajkovic SM, Wang CJ, Soeller C, Zimmermann H, Thorne PR, Housley GD
  
• Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8. Am J Physiol Gastrointest Liver Physiol. 2007; 292: G785–95
  Fausther M, Lecka J, Kukulski F, Lévesque SA, Pelletier J, Zimmermann H, Dranoff JA, Sévigny J
  
• Ectonucleotidases in Müller glial cells of the rodent retina: Involvement in inhibition of osmotic cell swelling. Purinergic Signal. 2007; 3: 423–33
  Iandiev I, Wurm A, Pannicke T, Wiedemann P, Reichenbach A, Robson SC, Zimmermann H, Bringmann A
  
• Ectonucleotidases, molecular properties and functional impact. An R Acad Nac Farm. 2007; 73: 537–66
  Zimmermann H, Mishra SK, Shukla V, Lange D, Gampe K, Grimm I, Delic J, Braun N
  
• The ectonucleotidases alkaline phosphatase and nucleoside triphosphate diphosphohydrolase 2 are associated with subsets of progenitor cell populations in the mouse embryonic, postnatal and adult neurogenic zones. Neuroscience. 2007; 150: 863–79
  Langer D, Ikehara Y, Takebayashi H, Hawkes R, Zimmermann H
  
• Capillary electrophoresis-based nanoscale assays for monitoring ecto-5`-nucleotidase activity and inhibition in preparations of recombinant enzyme and melanoma cell membranes. Analyt Biochem. 2008; 373: 129–40
  Iqbal J, Jirovsky D, Lee SJ, Zimmermann H, Müller CE
  
• Commentary: ATP and acetylcholine, equal brethren. Neurochem Int. 2008; 52: 634–48
  Zimmermann H
  
• Distribution of ectonucleotidasesin the rodent brain revisited. Cell Tissue Res. 2008; 334: 199–217
  Langer D, Hammer K, Koszalka P, Schrader J, Robson S, Zimmermann H
  
• Purinergic receptor activation inhibits osmotic glial cell swelling in the diabetic rat retina. Exp Eye Res. 2008; 87: 385–93
  Wurm A, Inandiev I, Hollborn M, Wiedemann P, Reichenbach A, Zimmermann H, Bringmann A, Pannicke T
  
• Coordinate pathways for nucleotide and EGF signaling in cultured adult neural progenitor cells. J Cell Sci. 2009; 122: 2524–33
  Grimm I, Messemer N, Stanke M, Gachet C, Zimmermann H
  
• Purinergic Signaling in the nervous system: an overview. Trends Neurosci. 2009; 32: 19–29
  Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H
  
• Structure-activity relationships of anthraquinone derivatives derived from bromaminic acid as inhibitors of ectonucleoside triphosphate diphosphohydrolases (E-NTPDases). Purinergic Signal. 2009; 5: 91–106
  Baqi Y, Weyler S, Iqbal J, Zimmermann H, Müller CE
  
• The expanding field of purinergic signaling Trends Neurosci. 2009; 32: 1
  Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H
  
• Trophic functions of nucleotides in the central nervous system. Trends Neurosci. 2009; 32: 189–198
  Neary JT, Zimmermann H