Melamine Disrupts Acetylcholine-Mediated Neural Information Flow in the Hippocampal CA3-CA1 Pathway.

Wei Sun,Peidong Liu,Lei An,Chunzhi Tang

doi:10.3389/fnbeh.2021.594907

Abstract

Considering the cognitive and synaptic deficits following intragastric administration of melamine, the aim of the current investigation was to test whether the hippocampal oscillations were affected. The local field potential (LFP) was recorded in the hippocampal CA3–CA1 pathway of Wistar rats during a spatial-dependent Y-maze task. The general partial directed coherence (gPDC) method was used to assess the directionality of neural information flow (NIF) between the CA3 and CA1 regions. The levels of acetylcholine (ACh) and its esterolytic protease, acetylcholinesterase (AChE), were detected in the hippocampus (HPC) following the behavioral test. The values of phase synchronization between the CA3 and CA1 regions in delta, low theta, and high theta oscillations were reduced significantly in the melamine-treated group. Moreover, the coupling directional index and the strength of CA3 driving CA1 were critically decreased in the above three frequency bands as well. Meanwhile, a reduction in ACh expression and an enhancement in AChE activity were found in the HPC of melamine-treated rats. Intrahippocampal infusion with ACh could mitigate the weakened neural coupling and directional NIF in parallel with spatial learning improvements. However, infusion of scopolamine, an acetylcholine receptor antagonist, could block the mitigative effects of ACh treatment in melamine rats. These findings provide first evidence that ACh-mediated neuronal coupling and NIF in the CA3–CA1 pathway are involved in spatial learning deficits induced by chronic melamine exposure.

Highlights

Melamine is a triazine heterocyclic chemical and has been widely used in the manufacturing of plastics
We found that melamine reduced the expression of ACh in the hippocampus involved in the weakened neural information flow (NIF), as indicated by the intrahippocampal infusion of ACh that could effectively enhance the diminished phase synchronization and directional index of NIF induced by melamine treatment, leading to the improvement of spatial learning performance in the Y-maze task
Compared to vehicle treatment of the control group, a high concentration of melamine was found in the melamine group, which indicated that melamine could gather in the HPC (t14 = 30.8, 31.05 ± 0.53 vs. 0.19 ± 0.03 μg/g, P = 0.000; Figure 2A)

Summary

Introduction

Melamine is a triazine heterocyclic chemical and has been widely used in the manufacturing of plastics. It cannot be used as an additive, melamine is approved as a food-content substance. Melamine induced pathological changes in HPC neurons such as the dense chromatin and shrinkage occurred mainly due to the formation of insoluble metabolites in cells (Wang et al, 2011; An and Zhang, 2014b, 2016; An et al, 2014). Further studies implied that melamine contamination during the prenatal period could inhibit the activation of postsynaptic receptors, thereby affecting hippocampal synaptic plasticity in the CA3–CA1 pathway, leading to cognitive deficits (An and Zhang, 2014a; An and Sun, 2017b,c). The underlying molecular mechanism of the destructive effects of melamine on the CA3–CA1 pathway is still unknown

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Results

Conclusion