Magnetic resonance imaging detects cerebral gray and white matter injury correlated with cognitive impairments in diabetic db/db mice

Abstract

Type-2 diabetes not only causes gray matter injury but also induces widespread white matter damages, which may contribute the cognitive impairments. This study aimed to assess the structural alterations of the gray and white matter in 20-week-old diabetic db/db mice using magnetic resonance imaging including T2-weighted imaging (T2WI) and diffusion tensor imaging (DTI), and to correlate them with the cognitive performance detected by Morris water maze (MWM). The results revealed impaired spatial learning and memory in db/db mice. T2WI detected severe brain atrophy involving the hippocampus and cortex after diabetes. DTI showed reduced fractional anisotropy (FA) in the cortex, hippocampus, corpus callosum/external capsule, and increased radial diffusivity in the corpus callosum/external capsule of the db/db mice. The immunostaining confirmed the MRI findings showing decreased cell density in the cortex, hippocampus, and reduced integrated optical density of Luxol fast blue staining in the corpus callosum/external capsule. The correlational analysis revealed that the T2WI-derived tissue atrophy and DTI-derived FA in the relevant gray matter and white matter significantly correlated with the behavior performance in the MWM test. Collectively, the present in vivo MRI detected varying degrees of structural abnormalities in the gray and white matter of db/db mice, which might be favorable predictors of diabetic cognitive dysfunction. Our findings might provide new clues for identifying gray and white matter damages associated with cognitive decline, which is imperative for the evaluation of potential pharmacological therapies in preclinical phase.