NT2 derived neuronal and astrocytic network signalling

Hill, Eric, Jiménez-González, Maria, Tarczyluk, Marta, Nagel, David A., Coleman, Mike D. and Parri, Rheinallt (2012). NT2 derived neuronal and astrocytic network signalling. PLoS ONE, 7 (5),

Abstract

A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns) expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As) exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality.

Publication DOI: https://doi.org/10.1371/journal.pone.0036098
Divisions: Life & Health Sciences
Life & Health Sciences > Biosciences
Life & Health Sciences > Chronic and Communicable Conditions
Life & Health Sciences > Pharmacy
Life & Health Sciences > Clinical and Systems Neuroscience
Life & Health Sciences > Cellular and Molecular Biomedicine
Additional Information: © 2012 Hill et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords: Agricultural and Biological Sciences(all),Biochemistry, Genetics and Molecular Biology(all),Medicine(all)
Full Text Link: http://www.plos ... al.pone.0036098
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2012-05-02
Authors: Hill, Eric ( 0000-0002-9419-1500)
Jiménez-González, Maria
Tarczyluk, Marta
Nagel, David A.
Coleman, Mike D.
Parri, Rheinallt ( 0000-0002-1412-2688)

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