IntroductionExercise and metabolic health are key modulators of brain plasticity, influencing processes such as angiogenesis and neurogenesis.MethodsThe present study investigated the effects of eight weeks of high-intensity interval training on capillary density and neurogenesis in the hippocampus of diabetic (db/db) and non-diabetic (db/+) mice, using established markers for capillaries (collagen IV) and immature neurons (doublecortin) through a series of immunolabelling experiments on fixed brain tissue.ResultsWe show that exercise significantly enhanced capillary density in the dentate hilus of diabetic mice, while having no effect in non-diabetic mice. Conversely, neurogenesis in the subgranular zone was increased by exercise in non-diabetic mice but remained unaffected in their diabetic littermates. Furthermore, correlation analyses challenge the dogma that angiogenesis directly promotes neurogenesis. We found no effect of either exercise or genotype on capillary density in the stratum radiatum or neurogenesis in the ventricular-subventricular zone, indicating a regional specificity of these processes.DiscussionThese findings challenge and nuance established concepts of cerebral angiogenesis and adult neurogenesis, and their regulation in response to T2D and physical exercise Understanding these differential responses to exercise provides new insights into cerebral effects of diabetes and may lay the foundation for tailoring interventions to optimize brain health in individuals with metabolic disorders.