Effects of mastication on hippocampal neurons as well as learning and memory ability

老年斑（senile plaques，SP）β淀粉样蛋白（Amyloid β，Aβ）是阿尔茨海默病（Alzheimer's disease，AD）的重要神经病理改变，其沉积和神经元丢失是AD病理级联反应的基础。虽然Aβ沉积的机制仍不清楚，但提示AD脑中Aβ蛋白的清除活性可能受损。以往研究表明，小胶质细胞可以通过释放金属蛋白酶或吞噬作用清除Aβ，提示小胶质细胞可能在阻止Aβ在中枢神经系统（CNS）沉积中发挥重要作用。另一方面，据报道，由于缺乏功能性巨噬细胞集落刺激因子（M-CSF），骨硬化（OP/OP）无牙小鼠中的小胶质细胞数量减少。咀嚼功能受损可引起海马神经元变性。本研究旨在观察op/op小鼠脑内Aβ沉积和海马神经元数量的变化。在op/op小鼠的大脑皮质、海马、杏仁核和下丘脑中检测到大量成熟的Sps，而在正常小鼠中未观察到定量证据。此外，在CA 1和CA 3区的锥体细胞的数量显着减少，在OP/OP小鼠比对照组。研究表明，在生理条件下，Aβ沉积和咀嚼减少影响神经元的丢失，SP的表达可能部分受小胶质细胞的调节。

Amyloid β(Aβ) protein of senile plaques (SPs) is a neuropathological change which characterize Alzheimer's disease (AD), and its deposition and neuron loss are essential for the pathological cascade of the disease. Although the mechanism of Aβ deposition still remains unclear, it is suggested that a clearance activity for the Aβ protein may be impaired in AD's brain. Previous studies demonstrated that microglia could remove Aβ by releasing a metalloprotease or by phagocytosis, suggesting that microglia may play an important role in preventing Aβ deposition in the central nervous system (CNS). On the other hand, it was reported that the number of microglia was reduced in osteopetrotic (op/op) toothless mice resulting from the lack of functional macrophage colony-stimulating factor (M-CSF). It was also exhibited that impairment of masticatory function caused degeneration of hippocampal neurons. The present study was thus designed to examine the Aβ deposition and the number of hippocampal neurons in the brain of op/op mice. A number of mature Sps were detected in the cerebral cortex, hippocampus, amygdala and hypothalamus in op/op mice, however, no quantitative evidence of Aβ deposition was observed in normal mice. Moreover, the number of pyramidal cells in the CA1, and CA3 regions was significantly reduced in op/op mice than in the controls. It is shown that Aβ deposition and reduced mastication influence the neuron loss and expression of SPs may be in part regulated by microglia under a physiological conditions.