Neural Regeneration Research ›› 2014, Vol. 9 ›› Issue (22): 1985-1994.doi: 10.4103/1673-5374.145380

Previous Articles     Next Articles

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.

PDF

947

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