Prenatal cyanuric acid exposure disrupts cognitive flexibility and mGluR1-mediated hippocampal long-term depression in male rats
| Autor: | Wei Sun, Yang Yang, Xiao Chen, Yazi Mei, Xiaoliang Li, Lei An |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Male
Neuronal Plasticity Depression Triazines Long-Term Synaptic Depression Long-Term Potentiation General Medicine Toxicology Alkaline Phosphatase Receptors Metabotropic Glutamate Hippocampus Rats Cognition Pregnancy Prenatal Exposure Delayed Effects Animals Humans Female alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid |
| Zdroj: | Toxicology letters. 370 |
| ISSN: | 1879-3169 |
| Popis: | Cyanuric acid is one of the most widely used classes of industrial chemicals and is now well known as food adulterant and contaminant in pet food and infant formula. Previously, it was reported that animals prenatally exposed to cyanuric acid showed neurotoxic effects that impaired memory consolidating and suppressed long-term potentiation (LTP) in the hippocampus. However, it is not clear if prenatal exposure to cyanuric acid induces deficits in reversal learning and long-term depression (LTD), which is required for the developmental reorganization of synaptic circuits and updating learned behaviors. Here, pregnant rats were i.p. injected with cyanuric acid (20 mg/kg) during the whole of gestation, and male offspring were selected to examine the levels of hippocampal mGluR1 and mGluR2/3 in young adulthood. The LTD at the Schaffer collateral-CA1 pathway was induced by low-frequency stimulation (LFS) and recorded. Reversal learning and hippocampus-dependent learning strategy were tested in Morris-water maze (MWM) and T-maze tasks, respectively. To further confirm the potential mechanism, selective agonists of mGluR1 and mGluR2/3 and antagonists of mGluR were intra-hippocampal infused before behavioral and neuronal recording. We found the levels of alkaline phosphatase were markedly increased in the maternal placenta and fetal brain following prenatal exposure. The expression of mGluR1 but not mGluR2/3 was significantly decreased and mGluR1-mediated LTD was selectively weakened. Prenatal cyanuric acid impaired reversal learning ability, without changing place learning strategy. The mGluR1 agonist could effectively enhance LFS-induced LTD and mitigate reversal learning deficits. Meanwhile, the reductions in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR)-mediated spontaneous excitatory postsynaptic currents (sEPSCs) amplitude and frequency of cyanuric acid offspring were simultaneously alleviated by mGluR1 agonist infusions. Therefore, the results indicate the cognitive and synaptic impairments induced by prenatal cyanuric acid exposure are attributed to the disruption of the hippocampal mGluR1 signaling. Our findings provided the first evidence for the deteriorated effects of cyanuric acid on synaptic depression and advanced cognitive performance. |
| Databáze: | OpenAIRE |
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