Astaxanthin Improved the Cognitive Deficits in APP/PS1 Transgenic Mice Via Selective Activation of mTOR
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ORIGINAL ARTICLE
Astaxanthin Improved the Cognitive Deficits in APP/PS1 Transgenic Mice Via Selective Activation of mTOR Cuiqin Huang 1 & Caiyan Wen 1 & Mei Yang 1 & An Li 1 & Chongzhu Fan 1 & Danhui Gan 1 & Qin Li 1 & Jiayi Zhao 1 & Lihong Zhu 1 & Daxiang Lu 1 Received: 22 March 2020 / Accepted: 26 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Astaxanthin (Ast) is an effective neuroprotective and antioxidant compound used to treat Alzheimer’s disease (AD); however, the underlying in vivo molecular mechanisms remain unknown. In this study, we report that Ast can activate the mammalian target of rapamycin (mTOR) pathway in the 8-month-old APP/PS1 transgenic mouse model of AD. Our results suggest that Ast could ameliorate the cognitive defects in APP/PS1 mice by activating the mTOR pathway. Moreover, mTOR activation perturbed the mitochondrial dynamics, increased the synaptic plasticity after 21 days of treatment with Ast (10 mg/kg/day), and increased the expression of Aβ-degrading enzymes, mitochondrial fusion, and synapse-associated proteins and decreased the expression of mitochondrial fission proteins. Intraperitoneal injection of the mTOR inhibitor, rapamycin, abolished the effects of Ast. In conclusion, Ast activates the mTOR pathway, which is necessary for mitochondrial dynamics and synaptic plasticity, leading to improved learning and memory. Our results support the use of Ast for the treatment of cognitive deficits. Keywords Alzheimer’s disease. astaxanthin. mitochondrial fusion. mitochondrial fission. synaptic plasticity
Introduction Alzheimer’s disease (AD), one of the most common neurodegenerative diseases, is characterized by the deposition of amyloid beta (Aβ) plaques, the formation of neurofibrillary tangles, and loss of neurons in the brain, leading to learning and memory disorders (Høgh 2017; Yilmaz 2015). Aβ (1–42) peptide, the major component of senile plaques, is toxic to neuronal cells and is considered to play a causative role in the development and progression of AD (Qu et al. 2011). Mammalian target of rapamycin (mTOR) is a serineElectronic supplementary material The online version of this article (https://doi.org/10.1007/s11481-020-09953-4) contains supplementary material, which is available to authorized users. Cuiqin Huang, Caiyan Wen and Mei Yang contributed equally to this work. * Daxiang Lu [email protected] 1
Department of Pathophysiology, Institute of Brain Science Research, Key Laboratory of State Administration of Traditional Chinese Medicine of the People’s Republic of China, School of Medicine, Jinan University, 510632 Guangzhou, Guangdong, China
threonine kinase that regulates several important aspects of mammalian mitochondrial dynamics, protein synthesis, and cell function (Hung et al. 2012; Laplante and Sabatini 2012). The mTOR pathway is important for the acquisition and maintenance of memory paradigms, including spatial, social, and motor functions (Chen et al. 2019). Although the molecular mechanism underlying AD development and
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