The Role of Cellular Metabolites in Neuronal Excitability in Health and Disease

This Research Topic aims to explore how cellular metabolites (intermediates or end-products of metabolic processes) influence neuronal activity in both healthy and pathological states, with a particular focus on excitability-related disorders (including but not limited to epilepsy, genetic metabolic disorders with epileptic manifestations, fragile X syndrome, migraine, Alzheimer’s disease and traumatic brain injury). While metabolites have been commonly studied under the lens of energetics, this Research Topic focuses on the contributions of individual metabolites to their role in modulating excitability. With this Collection, we aim to uncover the mechanisms by which metabolic shifts directly impact neuronal activity and contribute to conditions characterized by altered excitability, such as epilepsy, GLUT1 deficiency syndrome, and other metabolic epilepsies. Examples of metabolic products include, and are not limited to, lactate, pyruvate, ketone bodies, triglycerides (i.e., decanoic acid), NADP+/NADPH, ROS, as well as microbiota-derived metabolites. This Research Topic excludes canonical neurotransmitters (e.g., GABA, glutamate) and common neuromodulators (e.g., ATP, adenosine, serine), as extensive literature on their roles in neuronal function is already available.The primary objectives include but are not limited to:• Investigating how specific cellular metabolites regulate neuronal excitability in physiological conditions.• Investigating cell-specific metabolite effects (i.e., inhibitory vs excitatory). • Impact of microbiome-derived metabolic products on neuronal activity. • Techniques for simultaneously measuring metabolites and neuronal activity to gain deeper insights into their dynamic interactions.• Investigating how specific cellular metabolites are impacted in excitability-related disorders (including but not limited to epilepsy, genetic metabolic disorders with epileptic manifestations, fragile X syndrome, migraine, Alzheimer’s disease and traumatic brain injury). • Identifying metabolite-driven pathways that could serve as therapeutic targets for restoring normal neuronal function in pathological states.By addressing these questions, this Research Topic complements broader neuroenergetic studies by uncovering new aspects of how metabolism influences neuronal excitability. This topic not only highlights the unique role of metabolites in health and disease but also provides a foundation for developing precision-based interventions tailored to excitability-related disorders. We welcome submissions of the following article types: Original Research, Brief Research Report, Data Analysis, Editorial, General Commentary, Hypothesis & Theory, Methods, Mini Review, Perspective, Review, Systematic Review. Topic editors: Mattia Bonzanni, Thomas J Papouin, Alice Braga Source: https://www.frontiersin.org/research-topics/72683/the-role-of-cellular-metabolites-in-neuronal-excitability-in-health-and-disease