Functional astrocyte-neuron lactate shuttle in a human stem cell-derived neuronal network

Abstract

The NT2.D1 cell line is one of the most well-documented embryocarcinoma cell lines, and can be differentiated into neurons and astrocytes. Great focus has also been placed on defining the electrophysiological properties of the neuronal cells, and more recently we have investigated the functional properties of their associated astrocytes. We now show for the first time that human stem cell-derived astrocytes produce glycogen and that co-cultures of these cells demonstrate a functional astrocyte-neuron lactate shuttle (ANLS). The ANLS hypothesis proposes that during neuronal activity, glutamate released into the synaptic cleft is taken up by astrocytes and triggers glucose uptake, which is converted into lactate and released via monocarboxylate transporters for neuronal use. Using mixed cultures of NT2-derived neurons and astrocytes, we have shown that these cells modulate their glucose uptake in response to glutamate. Additionally, we demonstrate that in response to increased neuronal activity and under hypoglycaemic conditions, co-cultures modulate glycogen turnover and increase lactate production. Similar results were also shown after treatment with glutamate, potassium, isoproterenol, and dbcAMP. Together, these results demonstrate for the first time a functional ANLS in a human stem cell-derived co-culture. © 2013 ISCBFM.

Publication DOI: https://doi.org/10.1038/jcbfm.2013.81
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Uncontrolled Keywords: astrocyte,glycogen,lactate,neuron,stem cell,Cardiology and Cardiovascular Medicine,Clinical Neurology,Neurology
Full Text Link: http://www.natu ... bfm201381a.html
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2013-09
Published Online Date: 2013-05-29
Authors: Tarczyluk, Marta A.
Nagel, David A.
O'Neil, John
Parri, H. Rheinallt (ORCID Profile 0000-0002-1412-2688)
Tse, Erin H.Y.
Coleman, Michael D. (ORCID Profile 0000-0002-5510-6852)
Hill, Eric J. (ORCID Profile 0000-0002-9419-1500)

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