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

Marta A. Tarczyluk, David A. Nagel, John O'Neil, H. Rheinallt Parri, Erin H.Y. Tse, Michael D. Coleman, Eric J. Hill

Research output: Contribution to journalArticle

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.

LanguageEnglish
Pages1386-1393
Number of pages8
JournalJournal of Cerebral Bood Fow and Metabolism
Volume33
Issue number9
Early online date29 May 2013
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Astrocytes
Lactic Acid
Stem Cells
Neurons
Coculture Techniques
Glutamic Acid
Glycogen
Glucose
Cell Line
Isoproterenol
Hypoglycemic Agents

Keywords

  • astrocyte
  • glycogen
  • lactate
  • neuron
  • stem cell

Cite this

@article{5cf7dc277aa44fc3b8277be4dc17c001,
title = "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. {\circledC} 2013 ISCBFM.",
keywords = "astrocyte, glycogen, lactate, neuron, stem cell",
author = "Tarczyluk, {Marta A.} and Nagel, {David A.} and John O'Neil and Parri, {H. Rheinallt} and Tse, {Erin H.Y.} and Coleman, {Michael D.} and Hill, {Eric J.}",
year = "2013",
month = "9",
doi = "10.1038/jcbfm.2013.81",
language = "English",
volume = "33",
pages = "1386--1393",
journal = "Journal of Cerebral Bood Fow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "9",

}

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.; Hill, Eric J.

In: Journal of Cerebral Bood Fow and Metabolism, Vol. 33, No. 9, 09.2013, p. 1386-1393.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Functional astrocyte-neuron lactate shuttle in a human stem cell-derived neuronal network

AU - Tarczyluk, Marta A.

AU - Nagel, David A.

AU - O'Neil, John

AU - Parri, H. Rheinallt

AU - Tse, Erin H.Y.

AU - Coleman, Michael D.

AU - Hill, Eric J.

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - astrocyte

KW - glycogen

KW - lactate

KW - neuron

KW - stem cell

UR - http://www.scopus.com/inward/record.url?scp=84883741567&partnerID=8YFLogxK

U2 - 10.1038/jcbfm.2013.81

DO - 10.1038/jcbfm.2013.81

M3 - Article

VL - 33

SP - 1386

EP - 1393

JO - Journal of Cerebral Bood Fow and Metabolism

T2 - Journal of Cerebral Bood Fow and Metabolism

JF - Journal of Cerebral Bood Fow and Metabolism

SN - 0271-678X

IS - 9

ER -