Seizures and Amyloid-β induce similar changes in neuronal network metabolic parameters in mouse hippocampal slices

Major risk factors for neurodegenerative diseases share brain hypometabolism as one common outcome. In turn, many neurodegenerative pathologies result in brain hypometabolism; both epilepsy and Alzheimer's disease are characterised by disruptions in glucose metabolism. However, the causative link between energy shortage and neuronal pathologies in these disease has remained elusive. Using real-time brain slice recordings of energy metabolism parameter (NAD(P)H, FAD, pO2 and extracellular glucose) transients in response to network activation, we found that induced epileptic seizures and amyloid-beta peptide both result in similar and long-lasting disruptions of neuronal energy metabolism, suggesting a common path of action. In addition, we found that in both cases, subsequent addition of pyruvate, the principal mitochondrial fuel possessing multiple neuroprotective properties, completely normalised the disputed energy state. Our data suggests that energy metabolism disruptions underlie the initiation and progression of neurodegenerative diseases.