CHANGE IN SPATIAL MEMORY AND HIPOCAMPAL EXPRESSION OF C-FOS PROTEIN AS A RESULTS OF IMPAIRED MASTICATION IN THE SENSCENCE-ACCELERATED MOUSE

在本研究中，我们通过检测衰老加速小鼠（SAM-P8）和抗衰老小鼠（SAM-R1）切断上磨牙（无磨牙）对海马c-fos蛋白（c-fos）表达和空间记忆的影响，来评估咀嚼减少对衰老相关记忆障碍神经元机制的影响。在Morris水迷宫实验中，完整的SAM-P8找到隐藏平台的逃逸潜伏期在前几天较长，此后与SAM-R1对照组基本相同。行为试验后（第10天）免疫组化分析显示，两组海马组织中c- fos免疫阳性细胞核密度不显著。然而，在无磨牙SAM-P8中，水迷宫的逃避潜伏期明显增加，c- fos免疫阳性核密度明显降低，其中CAl亚区影响最大，其次是CA3亚区，然后是齿状回。这些变化随着无磨牙状态持续时间的增加而变得更加明显。相比而言，无磨牙的SAM-R1在迷宫倾斜和c-Fos表达方面没有明显变化。此外，无磨牙状态对SAM-R1和SAM-PS小鼠海马区gmap阳性细胞密度均无影响。这些结果表明，咀嚼功能受损可能会导致与年龄相关的海马活动减少，这与记忆障碍有关。

In the present study, we evaluated the effect of reduced mastication on the neuronal mechanism responsible for age-related memory impairment, by examining the effects of the cutting off of the upper molars (molarless) on hippocampal expression of c-fos protein (c-Fos) and spatial memory in the senescence-accelerated mouse (SAM-P8) and the senescence-resistant mouse (SAM-R1). In the Morris water maze test, the escape latency for intact SAM-P8 to find the hidden platform was longer in the first several days and thereafter almost the same as that for the SAM-R1 control. Immunohistochemical analysis following this behavioral test (on day 10) revealed no significant density of c-Fos-immunopositive cell nuclei in the hippocampal formation between these two groups. However, in molarless SAM-P8, both a marked increase in escape latency in the water maze and a significant decrease in c-Fos-immunoposive nuclei density were seen, the greatest effect being found in the CAl subfield, followed by the CA3 subfield, then the dentate gyrus. These changes became more pronounced with the increasing duration of the molarless condition. In contrast, the molarless SAM-R1 did not show any significant changes in maze leaning and c-Fos expression. Furthermore, the molarless condition had no effect on GFAP-positive cell density in the hippocampal formation in either SAM-R1 or SAM-PS mice. These results suggest that impaired mastication may cause the age-related reduction in hippocampal activity, linked to impairment of memory.