Astrocyte Neuron Metabolic Coupling – The Role of Glycogen, Lactate and Ketone Bodies in Brain Energy Metabolism

The brain’s high energy demands require precise metabolic coordination, particularly through astrocyte-neuron coupling, to sustain functions like cognition and synaptic activity. This literature review synthesizes recent advancements in understanding the roles of glycogen, lactate, and ketone bodies in brain energy metabolism, focusing on their regulation by astrocytes and the neurovascular unit. A systematic PubMed search (2020–2025) analyzed peer-reviewed studies on metabolic pathways, cellular interactions, and clinical implications. Findings reveal that astrocytes store glycogen and produce lactate, which is shuttled to neurons via the astrocyte-neuron lactate shuttle, supporting energy needs during intense activity or glucose scarcity. Ketone bodies serve as alternative fuels, particularly in neurodegenerative diseases with glucose hypometabolism, offering therapeutic potential through ketogenic strategies. The blood-brain barrier regulates substrate delivery, with dysfunction linked to disorders like Alzheimer’s disease. Despite progress, gaps persist in elucidating molecular mechanisms of glycogenolysis and long-term ketogenic effects. Future research should leverage advanced imaging and clinical trials to address these gaps. This review highlights metabolic coupling’s role in brain health and its disruption in pathology, advocating for interdisciplinary efforts to develop targeted therapies, such as ketone-based interventions, to enhance neuroprotection and cognitive resilience. These insights pave the way for personalized approaches to metabolic and neurodegenerative disorders, with broad implications for neuroscience and clinical practice.