Abstract
The astrocyte-neuron lactate transfer shuttle (ANLS) is one of the important metabolic systems that provides a physiological infrastructure for glia-neuronal interactions where specialized architectural organization supports the function. Perivascular astrocyte end-feet take up glucose via glucose transporter 1 to actively regulate glycogen stores, such that high ambient glucose upregulates glycogen and low levels of glucose deplete glycogen stores. A rapid breakdown of glycogen into lactate during increased neuronal activity or low glucose conditions becomes essential for maintaining axon function. However, it fails to benefit axon function during an ischemic episode in white matter (WM). Aging causes a remarkable change in astrocyte architecture characterized by thicker, larger processes oriented parallel to axons, as opposed to vertically-transposing processes. Subsequently, aging axons become more vulnerable to depleted glycogen, although aging axons can use lactate as efficiently as young axons. Lactate equally supports function during aglycemia in corpus callosum (CC), which consists of a mixture of myelinated and unmyelinated axons. Moreover, axon function in CC shows greater resilience to a lack of glucose compared to optic nerve, although both WM tracts show identical recovery after aglycemic injury. Interestingly, emerging evidence implies that a lactate transport system is not exclusive to astrocytes, as oligodendrocytes support the axons they myelinate, suggesting another metabolic coupling pathway in WM. Future studies are expected to unravel the details of oligodendrocyte-axon lactate metabolic coupling to establish that all WM components metabolically cooperate and that lactate may be the universal metabolite to sustain central nervous system function.
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Acknowledgement
This work was supported by grants from National Institute of Aging (NIA) to SB and NINDS to SB and SB, as well as a gift from Rose Mary Kubik. Selva Baltan has previously published as Selva Tekkök. The authors thank Dr. Chris Nelson, medical writer, for his help editing this chapter.
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Bastian, C. et al. (2019). Role of Brain Glycogen During Ischemia, Aging and Cell-to-Cell Interactions. In: DiNuzzo, M., Schousboe, A. (eds) Brain Glycogen Metabolism. Advances in Neurobiology, vol 23. Springer, Cham. https://doi.org/10.1007/978-3-030-27480-1_12
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