Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism
Hasel, Philip (University of Edinburgh)
Dando, Owen (University of Edinburgh)
Jiwaji, Zoeb (University of Edinburgh)
Baxter, Paul (University of Edinburgh)
Todd, Alison C. (University of Edinburgh)
Heron, Samuel (University of Edinburgh)
Márkus, Nóra M. (University of Edinburgh)
McQueen, Jamie (University of Edinburgh)
Hampton, David W. (University of Edinburgh)
Torvell, Megan (University of Edinburgh)
Tiwari, Sachin S. (University of Edinburgh)
McKay, Sean (University of Edinburgh)
Eraso-Pichot, Abel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Zorzano Olarte, Antonio (Universitat de Barcelona)
Masgrau, Roser (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Galea, Elena (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Chandran, Siddharthan (University of Edinburgh)
Wyllie, David J. A. (University of Edinburgh)
Simpson, T. Ian (University of Edinburgh)
Hardingham, Giles E. (University of Edinburgh)

Fecha:	2017
Resumen:	The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte-neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte-neuron metabolic cooperation.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Nature communications, Vol. 8 (may 2017) , ISSN 2041-1723

DOI: 10.1038/ncomms15132
PMID: 28462931

17 p, 2.8 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Neurociències (INc)
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