Cellular prion protein expression in astrocytes modulates neuronal survival and differentiation

Authors

  • Flavia R. S. Lima,

    1. Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
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    • 1

      FRSL and CPA contributed equally to this work.

    • 2

      The present address of Flavia R. S. Lima is Laboratório de Morfogênese Celular, Departamento de Anatomia, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro.

  • Camila P. Arantes,

    1. Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
    2. Departamento de Bioquímica, Instituto de Química da Universidade de São Paulo, São Paulo, Brazil
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    • 1

      FRSL and CPA contributed equally to this work.

  • Angelita G. Muras,

    1. Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
    2. Centro de Tratamento e Pesquisa Hospital A. C. Camargo, São Paulo, Brazil
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  • Regina Nomizo,

    1. Centro de Tratamento e Pesquisa Hospital A. C. Camargo, São Paulo, Brazil
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  • Ricardo R. Brentani,

    1. Centro de Tratamento e Pesquisa Hospital A. C. Camargo, São Paulo, Brazil
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  • Vilma R. Martins

    1. Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
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Address correspondence and reprint requests to Dr Vilma R. Martins, Ludwig Institute for Cancer Research, Rua João Julião 245, 1A, 01323-903 São Paulo, Brazil. E-mail: vmartins@ludwig.org.br

Abstract

The functions of cellular prion protein (PrPC) are under intense debate and PrPC loss of function has been implicated in the pathology of prion diseases. Neuronal PrPC engagement with stress-inducible protein-1 and laminin (LN) plays a key role in cell survival and differentiation. The present study evaluated whether PrPC 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 PrPC-null animals. Remarkably, neuritogenesis was greatly diminished in co-cultures combining PrPC-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 PrPC-null astrocytes displayed a punctate distribution, and did not support neuronal differentiation. Additionally, secreted soluble factors from PrPC-null astrocytes promoted lower levels of neuronal survival than those secreted by wild-type astrocytes. PrPC and stress-inducible protein-1 were characterized as soluble molecules secreted by astrocytes which participate in neuronal survival. Taken together, these data indicate that PrPC 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.

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