Melamine induced spatial cognitive deficits associated with impairments of hippocampal long-term depression and cholinergic system in Wistar rats

Our previous studies reported that hippocampus was one of the target sites of melamine, by which the spatial cognition and hippocampal long-term potentiation (LTP) could be impaired. The aim of present study was to investigate whether cognitive behavior impairment induced by melamine was associated with the alteration of hippocampal long-term depression (LTD), and try to interpret the potential underlying mechanism. Wistar rats were used to establish an animal model and melamine administered at a dose of 300 mg/kg/day for 4 weeks. Water maze behavior and long-term depression (LTD) in hippocampal CA3-CA1 pathway were measured, followed by enzyme linked immunosorbent assay (ELISA), by which acetylcholine (ACh) level and acetylcholinesterase (AChE) activity were determined. Results showed that learning and reversal learning abilities were significantly impaired by melamine. The field excitatory postsynaptic potential (fEPSP) slopes were significantly higher in melamine group compared to that in control group. Furthermore, the function of cholinergic system was damaged associated with decreased Ach level and enhanced AChE activity in melamine-treated rats. It suggested that melamine induced abnormal inhibitory effect on synaptic plasticity of hippocampus, which partly resulted in reduced LTD and further damaged cognitive flexibility. Melamine could also induce dysfunctional cholinergic system, which was associated with the poor performance of animals in MWM (Morris water maze) tests. (c) 2012 Elsevier Inc. All rights reserved.