Abstract
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Objectives: Diabetes is a risk factor of Parkinson's disease. They share similar pathogenic pathways in mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, and alterations in metabolism. However, the pathogenetic relationship between these two diseases is unclear. Vesicular Monoamine Transporter type 2 (VMAT2) has proven as a useful imaging marker for quantification of dopaminergic integrity in Parkinson's disease. 18F-FP-(+)-DTBZ, which is a VMAT2 ligand, could apply to measure dopaminergic integrity. The aim of this study was to examine the effect of hyperglycemia on the expression of VMAT2 in striatal of hyperglycemic rat model. Methods:Experimental group of hyperglycemic rat model (n = 6) was established by intraperitoneal injection of Streptozotocin (65 mg/kg body weight) in male Wistar rats (200-250 g), and rats with saline injection were used as control group. 10 day after Streptozotocin and saline injection in these rats, PET/CT scans were performed at 60 min post intravenous injection of 18F-FP-(+)-DTBZ. Imaging data were analyzed using PMOD 3.4 software. The striatal specific uptake ratio (SUr) was calculated as [(uptake in striatum - uptake in cerebellum) /uptake in cerebellum]. Results: After 14 days intraperitoneal injection of Streptozotocin, glucose level in these rats increased from 5.32 ± 0.83 mmol/L to 24.4 ± 5.18 mmol/L (p < 0.01), compared with 5.12 ± 0.55 mmol/L to 5.55 ± 0.45 mmol/L of glucose level in control rats. Body weight decreased from 227.5 ± 4.84 g to 157.33 ± 19.99 g (p < 0.01) in hyperglycemic rats, but slightly increased body weight was observed from 219.83 ± 14.06 g to 238.00 ± 14.66 g in control rats. Meanwhile, PET quantitative analysis demonstrated significantly lower striatal uptake in hyperglycemic rats (SUr: 1.42 ± 0.52)than that in the control rats (SUr: 2.50 ± 0.40,p < 0.01) [Fig 1]. Conclusion: Significantly decreased 18F-FP-(+)-DTBZ uptake in the striatum was detected in hyperglycemic rats by Streptozotocin-treated, which indicated that hyperglycemia may reduce the expression of VMAT2 in striatum of rat brains. Fig 1. Representative 18F-FP-(+)-DTBZ PET imaging in the brains of control and hyperglycemic rats. All PET imagings were performed at 60 min post injection and coregistered to a PMOD T2 MRI template. (A) Wistar rat at 10 days after saline injection (B) Wistar rat at 10 days after Streptozotocin injection ST: striatum Research Support: This research project was supported by the National Natural Science Foundation of China ( No. 81571345 ), the Research Center on Aging and Medicine, Fudan University ( No: IDF151006 ), National Key Research and Development Program Foundation of China ( No: 2016YFC1306403 ), Natural Science Foundation and Major Basic Research Program of Shanghai(No: 16JC1420502), Natural Science Foundation and Major Basic Research Program of Shanghai(No: 16JC1420100), Program of the Shanghai Science and Technology Commission( No: 1751107103, 17411953500 ).