Published online Apr 15, 2021. doi: 10.4239/wjd.v12.i4.499
Peer-review started: December 11, 2020
First decision: January 11, 2021
Revised: January 12, 2021
Accepted: March 7, 2021
Article in press: March 7, 2021
Published online: April 15, 2021
The mechanisms of diabetes-associated cognitive dysfunction (DACD) have not been fully elucidated to date. Some studies proved that lower cerebral blood flow (CBF) in the hippocampus was associated with poor executive function and memory in type 2 diabetes mellitus (T2DM). Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor (VEGF) expression and CBF changes in humans and animal models. This study explored whether DACD was correlated with CBF alteration and VEGF expression in the hippocampus.
Our study aimed to assess the relationship among CBF alteration, VEGF expression in the hippocampus, and DACD. Our findings may help reveal the mechanisms of DACD. This study would help in the detection of DACD and guide treatment.
This study aimed to explore whether VEGF signaling in the hippocampus in the T2DM rat model was related to CBF (measured by three dimensional arterial spin labeling) and DACD.
Forty specific-pathogen-free grade Sprague-Dawley male rats were randomly divided into normal control and T2DM groups. The T2DM group was kept on a high-fat diet and then streptozotocin was administered by intraperitoneal injections to induce diabetes. The Morris water maze test was conducted to explore the learning performance and spatial memory ability of experimental rats. CBF measured by three dimensional arterial spin labeling was detected in the bilateral hippocampus. Immunofluorescence of VEGF in the bilateral hippocampus was performed, and VEGF expression was quantified with quantitative real-time PCR.
Our data indicated that the spatial learning memory ability in the T2DM group significantly decreased. An obvious reduction in CBF in rats with T2DM in the bilateral hippocampal area was observed. The expression of VEGF was lower in the T2DM group than in the control group. VEGF expression positively correlated with the CBF value in the hippocampus. A significant correlation was found between CBF and the spatial learning memory ability in the T2DM group.
The new theories of this study was low perfusion of the hippocampus was associated with DACD and decreased VEGF expression in the hippocampal area of rats in the T2DM group in long-term hyperglycemia. To the best of our knowledge, this was the first study to explore the relationship of DACD, VEGF expression, and CBF of the hippocampus.
Decreased CBF and low VEGF levels in the hippocampus might be risk factors for DACD. CBF measured by three dimensional arterial spin labeling might serve as a noninvasive imaging biomarker for detecting cognitive impairment associated with T2DM.