中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (22): 1985-1994.doi: 10.4103/1673-5374.145380

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

损伤三叉神经SAMP8小鼠学习记忆相关脑区胆碱能神经元减少及学习能力下降：存在年龄差异

  

  • 收稿日期:2014-10-20 出版日期:2014-11-25 发布日期:2014-11-25

Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

Yifan He 1, Jihong Zhu 1, 2, Fang Huang 1, Liu Qin 1, Wenguo Fan 1, Hongwen He 1   

  1. 1 Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong
    Province, China
    2 Huaihe Hospital, Henan University, Kaifeng, Henan Province, China
  • Received:2014-10-20 Online:2014-11-25 Published:2014-11-25
  • Contact: Hongwen He, Ph.D., Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510060, Guangdong Province, China, hehw@mail.sysu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81371107, 81470760; the Natural Science Foundation of Guangdong Province in China, No. S2013010015888; the Foundation of Open Laboratory of Sun Yat-sen University in China, No. KF201312; a grant from Translational Medicine Center, Guangdong Department of Science & Technology, No. 2011A080300002.

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摘要：

牙齿与中枢神经有直接联系的是三叉神经感觉传导通路，那么牙齿损害引起的中枢神经损害是否与三叉神经损害有关？为解决这一问题，文章拟研究三叉神经传导通路中重要的外周神经--下牙槽神经损伤对快速老化痴呆模型SAMP8小鼠的学习记忆相关脑区神经元的影响。实验选用SAMP8小鼠，分别于4月龄（中年）和7月龄（老年）时横断三叉神经传导通路中重要的外周神经--下牙槽神经，以相应鼠龄行假手术小鼠为对照组。中年小鼠分别于8月龄和11月龄，老年小鼠于11月龄时进行海马结构尼氏染色和乙酰胆碱酯酶（AchE）酶组织化学染色，基底前脑胆碱乙酰转移酶（ChAT）免疫组化染色，以及跳台和Y迷宫试验测试小鼠学习记忆能力。结果显示，与老年对照组小鼠比较，切断下牙槽神经的老年大鼠海马CA1区、CA3区锥体细胞层神经元数量明显减少；海马CA1、齿状回乙酰胆碱酯酶（AchE）阳性（胆碱能）神经纤维均明显减少；膈内侧核和斜角带垂直支胆碱乙酰转移酶（ChAT）免疫阳性（胆碱能）神经元数量明显减少；学习能力明显下降。切断下牙槽神经对中年小鼠学习记忆相关脑区胆碱能神经元和学习能力无明显影响，即其在8和11月龄上述指标与对应的中年对照组相近。研究结果提示，三叉神经损害可引起隔-海马胆碱能投射通路退变和海马锥体细胞神经元的丢失，进而引起学习能力降低，三叉神经损害对学习记忆相关脑区胆碱能神经元和学习能力的影响存在年龄差异，故若老年人出现三叉神经损伤时应慎用拔牙和神经损害性治疗，以延缓相关脑区胆碱能神经元减少所致的神经退行性疾病的发生。

关键词: 阿尔茨海默病, 三叉神经, 学习, 记忆, 海马CA1区, 海马CA3区, 齿状回, 基底前脑, 膈内侧核, 斜角带垂直支, 胆碱能神经元, 胆碱能纤维, 锥体细胞

Abstract:

The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and indicate that tooth extraction should be avoided in these populations.

Key words: nerve regeneration, Alzheimer’s disease, trigeminal nerve, learning, memory, hippocampal CA1, hippocampal CA3, dentate gyrus, basal forebrain, medial septal nucleus, vertical limb of the diagonal band, cholinergic neurons, cholinergic fibers, pyramidal cells, NSFC grants, neural regeneration