Banxia Xiexin decoction ameliorated cognition via the regulation ofinsulin pathways and glucose transporters in the hippocampus of APPswe/PS1dE9mice

摘要

Reduced glucose utilization and deficient energy metabolism that occur in the early stages of Alzheimer’s disease correlate with impaired cognition, and this information is evidence that Alzheimer’s disease is a metabolic disease that is associated with brain insulin/insulin-like growth factor resistance. This research aimed to investigate the effects of Banxia Xiexin decoction (BXD) on cognitive deficits in APPswe/PS1dE9 double transgenic mice and verify the hypothesis that BXD treatment improves cognitive function via improving insulin signalling, glucose metabolism and synaptic plasticity in the hippocampus of APPswe/PS1dE9 double transgenic mice. We used 3-month-old APPswe/PS1dE9 double transgenic mice as the case groups and wild-type littermates of the double transgenic mice from the same colony as the control group. Forty-five APPswe/PS1dE9 double transgenic mice were randomly divided into the model group, donepezil group and BXD group. The mice in the control and model groups were administered 0.5% carboxymethyl cellulose orally. The Morris water maze and step-down test were conducted to evaluate the cognitive performance of APPswe/PS1dE9 double transgenic mice after BXD treatment. Ultrastructure of synapses was observed in the hippocampal CA1 area. Proteins involved in insulinsignalling pathways and glucose transports in the hippocampus were assessedthrough immunohistochemical staining and western blot. After 3 monthsintervention, we found that BXD treatment improved cognitive performance and thesynaptic quantity and ultrastructure, restored insulin signalling and increasedthe expression of glucose transporter 1 (GLUT1) and GLUT3 levels. These findingssuggest that the beneficial effect of BXD on cognition may be due to theimprovement of insulin signalling, glucose metabolism and synapticplasticity.