Single cell transcriptomic analysis of cortical cell type composition underlying diabetes-associated cognitive decline

Type 2 diabetes (T2D) is associated with increased risk of cognitive decline although the precise underlying pathogenesis remains obscure. Based on the single-cell RNA sequencing approach applied to the cerebral cortex of a T2D mouse model (db/db), we identified novel regulatory mechanisms underlying diabetes-associated cognitive deficits. Our data adds detail to the highly complex neurovascular pathology associated with T2D and highlights key cell-specific deficits in mitochondrial bioenergetics linked to neuroinflammation, which underlie T2D-linked cognitive impairment. For scRNA-seq, mouse were sacrificed at 16 weeks of age. The cortex was dissected and dissociated using the papain dissociation system (Worthington, Lakewood, NJ) as per the manufacturer’s instructions.