Resolving metabolic deficits in neurodevelopmental disorders

 Wiring of the brain and information transfer between developing neurons is extremely energy demanding. Neuronal energy metabolism and wiring are frequently altered in neurodevelopmental disorders (NDDs). We use sophisticated microscopy to measure energy costs at synapses during healthy development and in models of neurodevelopmental disorders to better understand their underlying causes. The Lohmann lab at the Netherlands Institute for Neuroscience, experts in synapse development and NDD research, and Becker & Hickl, pioneers of optical systems for measuring metabolism, will join forces to better understand metabolic deficits in NDDs. We will perform quantitative, high resolution measurements of metabolic processes in identified cells in intact tissue using fluorescence lifetime imaging (FLIM). 

NDDs affect 2-5 % of the world’s population and thus about 360.000-900.000 patients in the Netherlands. NDDs can have serious impact on daily life, affect social interactions and cause cognitive deficits. NDDs have frequently been described as synapse disorders, since synaptic signaling is changed and these changes can cause behavioral and mental challenges. 

We will harness a FLIM system that is specifically designed for quantitatively measuring energy metabolism in neurons from the developing cortex of NDD mouse models. Using this system, we plan to identify the cellular mechanisms of energy logistics and metabolism at synapses and how compromised energy metabolism contributes to synaptic errors in NDDs. 

We expect that this study will delineate quantitative markers of metabolic deficits in NDD brain wiring and that these findings will show new avenues for NDD diagnosis and treatment in the future.