Sweet sixteen for ANLS.

Since its introduction 16 years ago, the astrocyte-neuron lactate shuttle (ANLS) model has profoundly modified our understanding of neuroenergetics by bringing a cellular and molecular resolution. Praised or disputed, the concept has never ceased to attract attention, leading to critical advances and unexpected insights. Here, we summarize recent experimental evidence further supporting the main tenets of the model. Thus, evidence for distinct metabolic phenotypes between neurons (mainly oxidative) and astrocytes (mainly glycolytic) have been provided by genomics and classical metabolic approaches. Moreover, it has become clear that astrocytes act as a syncytium to distribute energy substrates such as lactate to active neurones. Glycogen, the main energy reserve located in astrocytes, is used as a lactate source to sustain glutamatergic neurotransmission and synaptic plasticity. Lactate is also emerging as a neuroprotective agent as well as a key signal to regulate blood flow. Characterization of monocarboxylate transporter regulation indicates a possible involvement in synaptic plasticity and memory. Finally, several modeling studies captured the implications of such findings for many brain functions. The ANLS model now represents a useful, experimentally based framework to better understand the coupling between neuronal activity and energetics as it relates to neuronal plasticity, neurodegeneration, and functional brain imaging

Recent advances in (patho)physiology of astroglia

Our view of astrocytes in the operation of the brain is changing dramatically over the last 3 decades. Astroglial calcium excitability controls the release of gliotransmitters, which can occur at the tripartite synapse. Astrocytes not only modulate synaptic transmission by releasing and taking up transmitters, but also receiving neuronal signals that act upon astrocytic plasma membrane receptors. This process represents the bidirectional neurone-glia communication. Additionally, astrocytes play role in the regulation of blood flow as well as ion and water homeostasis. Many of the brain dysfunctions are primary astropathies, including hepatic encephalopathy and Alexander disease, while other brain malfunctions, such as epilepsy and Alzheimer disease, may have substantial astrocytic contribution. Thus, these star-shaped cells by their roles in (patho)physiology of the brain seem to live up to the expectation one can have from their given name – astrocyte