title: Cellular prion protein expression in astrocytes modulates neuronal survival and differentiation.
abstract: The functions of cellular prion protein (PrP(C)) are under intense debate and PrP(C) loss of function has been implicated in the pathology of prion diseases. Neuronal PrP(C) engagement with stress-inducible protein-1 and laminin (LN) plays a key role in cell survival and differentiation. The present study evaluated whether PrP(C) expression in astrocytes modulates neuron-glia cross-talk that underlies neuronal survival and differentiation. Astrocytes from wild-type mice promoted a higher level neuritogenesis than astrocytes obtained from PrP(C)-null animals. Remarkably, neuritogenesis was greatly diminished in co-cultures combining PrP(C)-null astrocytes and neurons. LN secreted and deposited at the extracellular matrix by wild-type astrocytes presented a fibrillary pattern and was permissive for neuritogenesis. Conversely, LN coming from PrP(C)-null astrocytes displayed a punctate distribution, and did not support neuronal differentiation. Additionally, secreted soluble factors from PrP(C)-null astrocytes promoted lower levels of neuronal survival than those secreted by wild-type astrocytes. PrP(C) and stress-inducible protein-1 were characterized as soluble molecules secreted by astrocytes which participate in neuronal survival. Taken together, these data indicate that PrP(C) expression in astrocytes is critical for sustaining cell-to-cell interactions, the organization of the extracellular matrix, and the secretion of soluble factors, all of which are essential events for neuronal differentiation and survival.
authors.affiliation: Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.
authors.forename: Flavia R S
authors.initials: FR
authors.lastname: Lima
authors.forename: Camila P
authors.initials: CP
authors.lastname: Arantes
authors.forename: Angelita G
authors.initials: AG
authors.lastname: Muras
authors.forename: Regina
authors.initials: R
authors.lastname: Nomizo
authors.forename: Ricardo R
authors.initials: RR
authors.lastname: Brentani
authors.forename: Vilma R
authors.initials: VR
authors.lastname: Martins
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D006360:Heat-Shock Proteins; D007797:Laminin; D018621:PrPC Proteins; C489791:Stip1 protein, mouse