title: The role of low levels of fullerene C60 nanocrystals on enhanced learning and memory of rats through persistent CaMKII activation.
abstract: Engineered nanomaterials are known to exhibit diverse and sometimes unexpected biological effects. Fullerene nanoparticles have been reported to specifically bind to and elicit persistent activation of hippocampal Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine kinase central to Ca(2+) signal transduction and critical for synaptic plasticity, but the functional consequence of that modulation is unknown. Here we show that low doses of fullerene C60 nanocrystals (Nano C60), delivered through intrahippocampal infusion and without any obvious cytotoxicity in hippocampal neuronal cells, enhance the long-term potentiation (LTP) of rats. Intraperitoneal injection of 320 μg/kg of Nano C60, once daily for 10 days, also enhanced spatial memory of rats in addition to an increase of LTP. In parallel, both the IH and IP administration of Nano C60 increased the autonomous activity and the level of threonine 286 (T286) autophosphorylation of CaMKII, enhanced post-synaptic AMPA/NMDA ratio, and triggered time-dependent activation of ERK and CREB. Our results reveal a striking and highly unexpected ability of Nano C60 in positively modulating learning and memory, an effect that is most likely manifested through locking CaMKII in an active conformation, and may have significant implications for the potential therapeutic applications of fullerene C60, a classic engineered nanomaterial.
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Miao
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Bian
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Jutao
authors.initials: J
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zha
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: lpwen@ustc.edu.cn.
authors.forename: Long-Ping
authors.initials: LP
authors.lastname: Wen
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: wming@ustc.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D037741:Fullerenes / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007858:Learning / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D037741:Fullerenes; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D017346:Protein Serine-Threonine Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C069837:fullerene C60
keywords: Autonomous activity; CaMKII; Fullerene C60 nanocrystals; Learning and memory; Long-term potentiation; Threonine 286