Brain Angiopathy and Impaired Glucose Logistics in Mice with Psychosis-related Higher Brain Dysfunction

Abstract Psychiatric disorders are considered to be associated with metabolic dysfunction; however, it is unclear whether our current high-sugar diet contributes to pathogenesis. We demonstrate that a high-sucrose diet during adolescence induces psychosis-related phenotypes, such as hyperactivity, poor working memory, impaired sensory gating, and disrupted interneuron function, particularly in mice deficient for glyoxalase-1, an enzyme involved in detoxification of sucrose metabolites. Further, the high-sucrose diet induced microcapillary impairment and reduced brain glucose uptake. Aspirin protected against this angiopathy, enhanced brain glucose uptake, and prevented abnormal behavioral phenotypes. The brains of patients with schizophrenia and bipolar disorder exhibited similar angiopathy. Psychiatric disorders are associated with microvascular brain damage, possibly due to various environmental stresses including metabolic stress.