Graphene Oxide Ameliorates the Cognitive Impairment Through Inhibiting PI3K/Akt/mTOR Pathway to Induce Autophagy in AD M
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ORIGINAL PAPER
Graphene Oxide Ameliorates the Cognitive Impairment Through Inhibiting PI3K/Akt/mTOR Pathway to Induce Autophagy in AD Mouse Model Fangxuan Chu1 · Kai Li1 · Xiaolin Li1 · Lanju Xu1 · Jie Huang2 · Zhuo Yang1 Received: 28 July 2020 / Revised: 31 October 2020 / Accepted: 4 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Alzheimer’s disease (AD) is a neurodegenerative disease of the central nervous system characterised by cognitive impairment. Its major pathological feature is the deposition of β-amyloid (Aβ) peptide, which triggers a series of pathological cascades. Autophagy is a main pathway to eliminate abnormal aggregated proteins, and increasing autophagy represents a plausible treatment strategy against relative overproduction of neurotoxic Aβ. Graphene oxide (GO) is an emerging carbonbased nanomaterial. As a derivative of graphene with neuroprotective effects, it can effectively increase the clearance of abnormally aggregated protein. In this article, we investigated the protective function of GO in an AD mouse model. GO (30 mg/kg, intraperitoneal) was administered for 2 weeks. The results of the Morris water maze test and the novel object recognition test suggested that GO ameliorated learning and memory impairments in 5xFAD mice. The long-term potentiation and depotentiation from the perforant path to the dentate gyrus in the hippocampus were increased with GO treatment in 5xFAD mice. Furthermore, GO upregulated the expression of synapse-related proteins and increased the cell density in the hippocampus. Our results showed that GO up-regulated LC3II/LC3I and Beclin-1 and decreased p62 protein levels in 5xFAD mice. In addition, GO downregulated the PI3K/Akt/mTOR signalling pathway to induce autophagy. These results have revealed the protective potential of GO in AD. Keywords Graphene oxide · Alzheimer’s disease · Autophagy · β-amyloid · Synaptic plasticity · Cognition Abbreviations AD Alzheimer’s disease Aβ β-Amyloid plaque DEP Depotentiation fEPSPs Field excitatory post-synaptic potentials GO Graphene oxide GQDs Graphene quantum dots Fangxuan Chu and Kai Li have the same contribution to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11064-020-03167-z) contains supplementary material, which is available to authorized users. * Zhuo Yang [email protected] 1
Medical School, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, College of Medicine, Nankai University, Tianjin 300071, China
Department of Mechanical Engineering, University College London, London, UK
2
IT Initial training LC3 Microtubule-associated light chain 3 LFS Low-frequency stimulation LTP Long-term potentiation mTOR Mammalian target of rapamycin MWM Morris water maze NOR Novel object recognition NR2B N-methyl-d-aspartate receptor 2B PD Parkinson’s disease PI3K Phosphatidylinositol-3 kinases PSD-95 Postsynaptic density protein 9
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