Propionate ameliorates diabetes-induced neurological dysfunction through regulating the PI3K/Akt/eNOS signaling pathway

Abstract

AbstractA large body of research has established diabetes-related cognitive deterioration, sometimes known as “diabetic encephalopathy.” Current evidence supports that oxidative stress, neuronal apoptosis, and cerebral microcirculation weakness are associated with cognition deficits induced by diabetes. The present study explores the effect of propionate on neurological deficits, cerebral blood flow, and oxidative stress in diabetic mice. Propionate can markedly improve neurological function, which is correlated with its capabilities of stimulating nitric oxide (NO) production, increasing cerebral microcirculation, suppressing oxidative stress and reducing neuron loss in the hippocampus. In addition, the results of Western Blotting indicated that the brain-protective function of propionate in streptozocin (STZ)-induced insulin-dependent diabetes mellitus (IDDM) mice is related to phosphoinositide 3-kinase (PI3K)/serine-threonine protein kinase (Akt)/endothelial nitric oxide synthase(eNOS) signaling pathway. In a diabetic mouse model, propionate reduces cerebral microcirculation, hippocampus apoptosis, and neurological impairment. Thus, propionate, now employed as a food preservative, may also help slow diabetes-induced cognitive loss.Graphical AbstractHighlightsPropionate ameliorates diabetic-induced depression-like behavior, spatial learning and memory deficits.Propionate increases cerebral microcirculation by enhancing NO production in diabetic mice.Propionate suppresses oxidative stress and reduces neuron loss in the hippocampus.The brain-protective function of propionate is related to PI3K/Akt/eNOS signaling pathway.