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.