Melamine impairs spatial cognition and hippocampal synaptic plasticity by presynaptic inhibition of glutamatergic transmission in infant rats

The scandal of melamine-contamination has not been quite blown out, since the toxicity of melamine continues to raise concerns for public health. It has been well known that fetus and infant periods play the most important roles in brain development, whereas little has been done on the harmful effects of melamine on the center nervous system (CNS) of children. In the present study, we investigated the effects of melamine on behavioral and electrophysiology alternations in rats, and the effects of melamine on synaptic transmission were examined using whole-cell patch-clamp technique in the hippocampal CA1 neurons of infant rats. Morris water maze (MWM) test showed that learning and memory abilities were impaired significantly by melamine. The long-time potentiation (LTP) test exhibited that the field excitatory postsynaptic potential (fEPSP) slopes were significantly lower in melamine group compared to that in control group. Furthermore, the data of whole-cell patch-clamp experiments showed that melamine decreased the frequencies of both spontaneous EPSCs (sEPSCs) and minitura EPSCs (mEPSCs) to the same extent (about 76% and 78% respectively). However, there were no significant changes in sEPSC or mEPSC amplitude or kinetics after melamine addition, indicating that the effect of melamine on glutamatergic transmission was probably presynaptic. In conclusion, melamine reduced the release of glutamate in presynaptic transmission of hippocampus, which partly resulted in diminished LTP and further damaged the function of learning and memory. (C) 2011 Elsevier Ireland Ltd. All rights reserved.