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14 February 2017 : Animal Research  

Evaluating the Effectiveness of GTM-1, Rapamycin, and Carbamazepine on Autophagy and Alzheimer Disease

Lijuan Zhang1CD, Lina Wang2E, Run Wang3F, Yuan Gao1C, Haoyue Che1BDE, Yonghua Pan1EF, Peng Fu1AG*

DOI: 10.12659/MSM.898679

Med Sci Monit 2017; 23:801-808

Abstract

BACKGROUND: This study was proposed to compare the efficacy and safety of GTM-1, Rapamycin (Rap), and Carbamazepine (CBZ) in managing Alzheimer disease (AD). The impact of the above mentioned therapeutic drugs on autophagy was also investigated in our study.

MATERIAL AND METHODS: Firstly, 3×Tg AD mice were randomly allocated into 4 groups (each group with 10 mice), in which AD mice were separately treated with dimethylsulfoxide (DMSO, vehicle group), GTM-1 (6 mg/kg), Rap (1 mg/kg), and CBZ (100 mg/kg). Then spatial memory and learning ability of mice was tested using the Morris water maze. Routine blood tests were performed to evaluate the toxicity of these drugs. Amyloid-β42 (Aβ42) concentration was detected by ELISA and immunohistochemistry. Proteins related to autophagy were detected by Western blot.

RESULTS: GTM-1, Rap, and CBZ significantly improved the spatial memory of 3×Tg AD mice compared to that in the vehicle group (all P<0.05). Moreover, this study revealed that CBZ dosage was related to toxicity in mice. All of the above drugs significantly increased the expression of LC3-II and reduced Aβ42 levels in hippocampi of 3×Tg AD mice (all P<0.05). On the other hand, neither GTM-1 nor CBZ had significant influence on the expression of proteins on the mTOR pathway.

CONCLUSIONS: GTM-1 can alleviate the AD syndrome by activating autophagy in a manner that is dependent on the mTOR pathway and it therefore can be considered as an alternative to Rap.

Keywords: Alzheimer Disease - pathology, Autophagy - drug effects, Carbamazepine - pharmacology, Hippocampus - pathology, Maze Learning - drug effects, Neurons - pathology, Neuroprotective Agents - pharmacology, Plaque, Amyloid - pathology, Quinazolines - pharmacology, Random Allocation, Sirolimus - pharmacology, Spatial Memory - drug effects

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750