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. 2011:6:1453-61.
doi: 10.2147/IJN.S18507. Epub 2011 Jul 11.

Nano-zinc oxide damages spatial cognition capability via over-enhanced long-term potentiation in hippocampus of Wistar rats

Dadong Han  1 , Yutao Tian, Tao Zhang, Guogang Ren, Zhuo Yang
Affiliations

Nano-zinc oxide damages spatial cognition capability via over-enhanced long-term potentiation in hippocampus of Wistar rats

Dadong Han et al. Int J Nanomedicine. 2011.

Abstract

This study focused on the effects of zinc oxide nanoparticles (nano-ZnO) on spatial learning and memory and synaptic plasticity in the hippocampus of young rats, and tried to interpret the underlying mechanism. Rats were randomly divided into four groups. Nano-ZnO and phosphate-buffered saline were administered in 4-week-old rats for 8 weeks. Subsequently, performance in Morris water maze (MWM) was determined, and then long-term potentiation (LTP) and depotentiation were measured in the perforant pathway to dentate gyrus (DG) in anesthetized rats. The data showed that, (1) in MWM, the escape latency was prolonged in the nano-ZnO group and, (2) LTP was significantly enhanced in the nano-ZnO group, while depotentiation was barely influenced in the DG region of the nano-ZnO group. This bidirectional effect on long-term synaptic plasticity broke the balance between stability and flexibility of cognition. The spatial learning and memory ability was attenuated by the alteration of synaptic plasticity in nano-ZnO-treated rats.

Keywords: depotentiation; long-term potentiation; memory; spatial learning; synaptic plasticity; zinc oxide nanoparticles.

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Figures

Figure 1
Figure 1
Transmission electron microscopy image of nanoscaled ZnO particles.
Figure 2
Figure 2
(A) Comparison of escape latency of acquisition phase between nano-ZnO-treated group and control group. (B) Comparison of percentage of escape latency in southwest quadrant between nano-ZnO-treated group and control group. Notes: Data are expressed as mean ± standard error of the mean; *P < 0.05 compared with control group; **P < 0.01 compared with control group. Abbreviation: nano-ZnO, zinc oxide nanoparticles.
Figure 3
Figure 3
(A) Comparison of temporal distribution of southeast quadrant in probe trial between nano-ZnO-treated group and control group. (B) Comparison of number of times crossing hidden platform in probe trial between nano-ZnO-treated group and control group. Notes: Data are expressed as mean ± standard error of the mean; *P < 0.05 compared with control group. Abbreviation: nano-ZnO, zinc oxide nanoparticles.
Figure 4
Figure 4
Comparison of escape latency of reacquision phase between nano-ZnOtreated group and control group. Notes: Data are expressed as mean ± standard error of the mean; *P < 0.05 compared with control group; **P < 0.01 compared with control group. Abbreviation: nano-ZnO, zinc oxide nanoparticles.
Figure 5
Figure 5
Comparison of percentages of escape latency in NW, NE, SW, and SE quadrant between nano-ZnO-treated group and control group in reacquision phase. Statistical significances were obtained in quadrant SW and NE. Notes: Data are expressed as mean ± standard error of the mean; *P < 0.05; **P < 0.01 compared with control group. Abbreviations: nano-ZnO, zinc oxide nanoparticles; NE, northeast; NW, northwest; SE, southeast; SW, southwest.
Figure 6
Figure 6
Electrophysiological data. LTP was induced using TBS, and depotentiation was induced using LFS after recording a stable baseline for 20 minutes. LTP lasted at least 90 minutes. (A) Comparison of slopes of EPSP of LTP and depotentiation in nano-ZnO-treated group and control group. (B) Last 20 minutes of LTP-evoked responses was normalized and used for the baseline responses of depotentiation. Comparison of slopes of EPSP of LTP and depotentiation in nano-ZnO-treated group and control groups. Notes: Data are expressed as mean ± standard error of the mean; **P < 0.01 compared with control group. Abbreviations: EPSP, excitatory postsynaptic potential; HFS, high frequency stimulation; LFS, low frequency stimulation; LTD, long-term depotentiation; LTP, long-term potentiation; nano-ZnO, zinc oxide nanoparticles; TBS, theta burst stimulation.
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