Functional astrocyte-neuron lactate shuttle in a human stem cell-derived neuronal network
| Autor: | Marta A. Tarczyluk, Erin H. Y. Tse, David A. Nagel, Michael D. Coleman, John D. O'Neil, Eric J. Hill, H. Rheinallt Parri |
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| Rok vydání: | 2013 |
| Předmět: |
Synaptic cleft
Glucose uptake Glutamic Acid Cell Communication Biology chemistry.chemical_compound Cell Line Tumor medicine Premovement neuronal activity Humans Lactic Acid Neurons Glycogen Glutamate receptor Coculture Techniques medicine.anatomical_structure Neurology chemistry Astrocytes Original Article Neurology (clinical) Neuron Stem cell Nerve Net Cardiology and Cardiovascular Medicine Neuroscience Astrocyte |
| Zdroj: | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 33(9) |
| ISSN: | 1559-7016 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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