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

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Abstract

The development of stem cell-derived neuronal networks will promote experimental system development for drug screening, toxicological testing and disease modelling, providing that they mirror closely the functional competencies of their in vivo counterparts. The NT2 cell line is one of the best documented embryocarcinoma cell lines, and can be differentiated into neurons and astrocytes. Great focus has also been placed on defining the electrophysiological properties of these cells, and more recently we have investigated the functional properties of their associated astrocytes. We now show for the first time in a human stem cell derived co-culture model that these cultures are also metabolically competent and 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, an effect that was blocked by cytochalasin B and ouabain. 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 following 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.

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Original languageEnglish
Publication statusUnpublished - 2013
EventFestival of neuroscience - Barbican Centre, London, United Kingdom
Duration: 7 Apr 201310 Apr 2013

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OtherFestival of neuroscience
Abbreviated titleBNA 2013
CountryUnited Kingdom
CityLondon
Period7/04/1310/04/13
OtherBritish Neuroscience Association

Bibliographic note

Biotechnology and Biological Sciences Research Council [BB/H008527/1]; Alzheimer's Research UK [PPG2009B-3]

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