Bisphenol A (BPA), an environmental xenoestrogen, has been reported to induce learning and memory impairments in rodent animals. However, effects of BPA exposure on synaptic plasticity and the underlying physiological mechanisms remain elusive. Our behavioral and electrophysiological analyses show that BPA obviously perturbs hippocampal spatial memory of juvenile Sprague–Dawley rats after four weeks exposure, with significantly impaired long-term potentiation (LTP) in the hippocampus. These effects involve decreased spine density of pyramidal neurons, especially the apical dendritic spine. Further presynaptic findings show an overt inhibition of pulse-paired facilitation during electrophysiological recording, which suggest the decrease of presynaptic transmitter release and is consistent with reduced production of presynaptic glutamate after BPA exposure. Meanwhile, LTP-related glutamate receptors, NMDA receptor 2A (NR2A) and AMPA receptor 1 (GluR1), are significantly downregulated in BPA-exposed rats. Excitatory postsynaptic currents (EPSCs) results also show that EPSCNMDA, but not EPSCAMPA, is declined by 40% compared to the baseline in BPA-perfused brain slices. Taken together, these findings reveal that juvenile BPA exposure has negative effects on synaptic plasticity, which result from decreases in dendritic spine density and excitatory synaptic transmission. Importantly, this study also provides new insights into the dynamics of BPA-induced memory deterioration during the whole life of rats.

Current studies have demonstrated the advantage of graphene-based materials, which suggests their potential usage for biomedical applications. However, the in vivo toxicity and performance of three-dimensional (3D) graphene foams (GFs) remain largely unclear. In the present study, we identified the short-term and long-term tissue responses to GFs or graphene oxide foams (GOFs) in a rat model of subcutaneous implantation. Results from blood biochemistry, hematological analysis, histological examination, and behavioral test all indicated nearly no noticeable in vivo toxicity in either GF- or GOF-implanted rats during the first 2 weeks post-implantation. In addition, hematoxylin and eosin (H and E) stained images showed GFs or GOFs remained in the subcutaneous implantation site for at least 7 months without significant degradation after implantation. Our study demonstrates the non-biodegradable feature of GFs and GOFs as implanted scaffolds, while they exhibit good biocompatibility in vivo. It adds new evidence for the in vivo toxicological study of GFs and GOFs, which may provide reference for their biomedical applications.

In a biological environment, nanoparticles encounter and interact with thousands of proteins, forming a protein corona on the surface of the nanoparticles, but these interactions are oftentimes perceived as nonspecific protein adsorption, with protein unfolding and deactivation as the most likely consequences. The potential of a nanoparticle–protein interaction to mimic a protein–protein interaction in a cellular signaling process, characterized by stringent binding specificity and robust functional modulation for the interacting protein, has not been adequately demonstrated. Here, we show that water-suspended fullerene C60 nanocrystals (nano-C60) interact with and modulate the function of the Ca2+/calmodulin-dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine kinase central to Ca2+ signal transduction, in a fashion that rivals the well-documented interaction between the NMDA (N-methyl-d-aspartate) receptor subunit NR2B protein and CaMKII. The stable high-affinity binding of CaMKII to distinct sites on nano-C60, mediated by amino acid residues D246 and K250 within the catalytic domain of CaMKIIα, but not the nonspecific adsorption of CaMKII to diamond nanoparticles, leads to functional consequences reminiscent of the NR2B–CaMKII interaction, including generation of autonomous CaMKII activity after Ca2+ withdrawal, calmodulin trapping and CaMKII translocation to postsynaptic sites. Our results underscore the critical importance of specific interactions between nanoparticles and cellular signaling proteins, and the ability of nano-C60 to sustain the autonomous kinase activity of CaMKII may have significant implications for both the biosafety and the potential therapeutic applications of fullerene C60.Keywords: amino acid residues; autonomous activity; Ca2+/CaM-dependent protein kinase II; fullerene C60 nanocrystals; NMDA receptor subunit NR2B protein; specific interaction; T286 autophosphorylation