About Dr. Frank W. Pfrieger
We are interested in neuron-glia interactions in the mammalian central nervous system. We focus on the retina, where we study the functions of Müller cells, radial glia-like cells that span across the retina and touch all retinal neurons. Currently, we are working on two projects.
First, we study the metabolism of cholesterol in the retina based on our working hypotheses are that retinal ganglion cells depend on the supply by Müller cells and that a breakdown of the cholesterol delivery causes their degeneration. We are testing these hypotheses in vitro using cultures of highly purified ganglion cells and in vivo using mice with a spontaneous mutation in the NPC1 protein, an endosomal/lysosomal component that mediates the intracellular redistribution of externally acquired cholesterol. Mutations in the Npc1 gene cause Niemann-Pick type C disease, a rare and fatal lysosomal storage disorder, which is characterized by visceral and neurologic symptoms.
Second, we address the physiologic relevance of "gliotransmission", which postulates that glial cells release molecules like glutamate via calcium-dependent vesicular release. To this end, we have developed new transgenic mice for temporally controlled and cell-specific block of exocytosis by targeted expression of a clostridial neurotoxin. We are using these mice to test whether inhibition of exocytosis in Müller cells affects retinal structure and function in vivo.
- Pfrieger FW, Barres BA (1997) Synaptic efficacy enhanced by glial cells in vitro. Science 277: 1684-1687.
- Mauch DH, Nägler K, Schumacher S, Göritz C, Müller EC, Otto A, Pfrieger FW (2001). CNS synaptogenesis promoted by glia-derived cholesterol. Science 294, 1354-1357.
- Pfrieger FW (2003) Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes? Bioessays 25: 72-78.0
- Slezak M, Goritz C, Niemiec A, Frisen J, Chambon P, Metzger D, Pfrieger FW (2007) Transgenic mice for conditional gene manipulation in astroglial cells. Glia 55: 1565-76.
- Nieweg K, Schaller H, Pfrieger FW (2009) Marked differences in cholesterol synthesis between neurons and glial cells from postnatal rats. J Neurochem 109: 125-34.
- Claudepierre T, Paques M, Simonutti M, Buard I, Sahel J, Maue RA, Picaud S, Pfrieger FW (2010) Lack of Niemann Pick type C1 induces age-related degeneration in the mouse retina. Mol Cell Neurosci 43: 164-176.
- Pfrieger FW, Ungerer N (2011) Cholesterol metabolism in neurons and astrocytes. Prog Lipid Res 50: 357-371.
- Pfrieger FW, Slezak M (2012) Genetic approaches to study glial cells in the rodent brain. Glia 60: 681-701.
- Slezak M, Grosche A, Niemiec A, Tanimoto N, Pannicke T, Münch TA, Crocker B, Isope P, Härtig W, Beck SC, Huber G, Ferracci G, Perraut M, Reber M, Miehe M, Demais V, Lévêque C, Metzger D, Szklarczyk K, Przewlocki R, Seeliger MW, Sage-Ciocca D, Hirrlinger J, Reichenbach A, Reibel S, Pfrieger FW (2012) Relevance of exocytotic glutamate release from retinal glia. Neuron In press.
- Schultheiß C, Abe P, Hoffmann F, Mueller W, Kreuder AE, Schütz D, Haege S, Redecker C, Keiner S, Kannan S, Claasen JH, Pfrieger FW, Stumm R (2013) CXCR4 prevents dispersion of granule neuron precursors in the adult dentate gyrus. Hippocampus 23: 1345-1358.
- Mathis C, Savier E, Bott JB, Clesse D, Bevins N, Sage-Ciocca D, Geiger K, Gillet A, Laux-Biehlmann A, Goumon Y, Lacaud A, Lelièvre V, Kelche C, Cassel JC, Pfrieger FW, Reber M (2014) Defective response inhibition and collicular noradrenaline enrichment in mice with duplicated retinotopic map in the superior colliculus. Brain Struct Funct
- Buard I, Pfrieger FW (2014) Relevance of neuronal and glial NPC1 for synaptic input to cerebellar Purkinje cells. Mol Cell Neurosci 61: 65-71
- Transgenic mice
- Retinal preparations (e.g. whole-mount)
- Purification and culture of neurons and glial cells
- Electrophysiological recordings