Cellular prion protein expression in astrocytes modulates neuronal survival and differentiation

Autor(es)

Lima, Flavia R. S. ; Arantes, Camila P. ; Muras, Angelita G. ; Nomizo, Regina ; Brentani, Ricardo R. ; Martins, Vilma R. ^[6]

• Tipo de documento: Artigo Científico
• Fonte: Journal of Neurochemistry; v. 103, n. 6, p. 2164-2176, Dec. 2007.
• Área do conhecimento: Ciências Biológicas - Bioquímica
• Assunto(s): Neoplasias neuroepiteliomatosas Glioma Proliferação celular Proteínas Príons

Resumo

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. (AU)

• Processo FAPESP: 03/13189-2 - Papel da proteína prion celular em processos fisiológicos e patológicos II
• Beneficiário: Vilma Regina Martins
• Linha de fomento: Auxílio à Pesquisa - Temático