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

Tarczyluk, Marta A., Nagel, David A., O'Neil, John, Parri, H. Rheinallt, Tse, Erin H.Y., Coleman, Michael D. and Hill, Eric J. (2013). Functional astrocyte-neuron lactate shuttle in a human stem cell-derived neuronal network. Journal of Cerebral Bood Fow and Metabolism, 33 (9), pp. 1386-1393.

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: Life & Health Sciences > Biosciences
Life & Health Sciences > Pharmacy
Life & Health Sciences > Clinical and Systems Neuroscience
Life & Health Sciences
Life & Health Sciences > Chronic and Communicable Conditions
Life & Health Sciences > 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)
Published Date: 2013-09
Authors: Tarczyluk, Marta A.
Nagel, David A.
O'Neil, John
Parri, H. Rheinallt ( 0000-0002-1412-2688)
Tse, Erin H.Y.
Coleman, Michael D.
Hill, Eric J. ( 0000-0002-9419-1500)

Download

[img]

Version: Accepted Version


Export / Share Citation


Statistics

Additional statistics for this record