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Chronic Cyanuric Acid Exposure Depresses Hippocampal LTP but Does Not Disrupt Spatial Learning or Memory in the Morris Water Maze

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Abstract

Exposure to cyanuric acid (CA) causes multiple organ failure accompanied by the involvement in kinds of target proteins, which are detectable and play central roles in the CNS. The hippocampus has been identified as a brain area which was especially vulnerable in developmental condition associated with cognitive dysfunction. No studies have examined the effects of CA on hippocampal function after in vitro or in vivo treatment. Here, we aimed to examine hippocampal synaptic function and adverse behavioral effects using a rat model administered CA intraperitoneally or intrahippocampally. We found that infusion of CA induced a depression in the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), miniature excitatory postsynaptic currents (mEPSCs), or N-methyl-D-aspartate (NMDA)-mediated excitatory postsynaptic currents (EPSCs) of the CA1 neurons in dose-dependent pattern. Both intraperitoneal and intrahippocampal injections of CA suppressed hippocampal LTP from Schaffer collaterals to CA1 regions. Paired-pulse facilitation (PPF), a presynaptic phenomenon, was enhanced while the total and phosphorylated expression of NMDA-GluN1, NMDA-GluN2A, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-GluA1 subunits were comparable between CA-treated and control groups. In Morris water maze test, both groups could effectively learn and retain spatial memory. Our studies provide the first evidence for the neurotoxic effect of CA and the insight into its potential mechanisms.

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This work was supported by Grants from the National Natural Science Foundation of China (31700929) to LA.

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Sun, W., Yang, Y., Wu, Z. et al. Chronic Cyanuric Acid Exposure Depresses Hippocampal LTP but Does Not Disrupt Spatial Learning or Memory in the Morris Water Maze. Neurotox Res 39, 1148–1159 (2021). https://doi.org/10.1007/s12640-021-00355-9

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