课程名称︰分子神经病理学 课程性质︰选修 课程教师︰廖永丰/陈志成 开课学院：生命科学院 开课系所︰生命科学系 考试日期（年月日）︰2018/04/19 考试时限（分钟）：180 min 试题 : Please answer the following questions concisely. Each question is worth 10 pts. (Open-book exam) 廖永丰部分 1. (i) Glutamate could be a neurotransmitter and an initiator of excitotoxicity in neurodegeneration. NMDA receptor-mediated excessive Ca2+ influx and resultant overstimulation of nNOS activity are key events leading to neuronal death. How does memantine manifest less side effects, comparing to other NMDA receptor antagonists, as an advantageous drug for neruo- degenerative diseases? (5 pts.) (ii) Please describe a possible scenario in which the non-apoptotic caspases can contribute to the NMDA receptor-mediated long-term depression in learning and memory. (5 pts.) 2. (i) Mutation in SOD1 have been linked to amyotrophic lateral sclerosis(ALS). Please describe one experimental result that defines the mutant SOD1- induced programmed cell death in spinal cord motor neurons. (5 pts.) (ii) Riluzole is the first FDA-approved drug for ALS, but its mechanism of action is poorly understood. Based on pathophysiology of ALS depicted in the suggested reading (20180315Ref), please propose a model in which which riluzole treatment can be effective on suppressing the ALS mutation-induced neuronal injury. (5 pts.) 3. (i) Prion Hypothesis states that PrPSc itself is the infectious agent and facilitates conversion of PrPC to PrPSc. The initial formation of PrPSc might be localized and followed by the propagation of PrPSc throughout the brain. Please explain why the PrPC-depleted mice can survive up to 48 weeks after inoculation. (5 pts) (ii) If you are designing a new chemical compound targeting prion disease, which one of PrPSc-mediated cellular pathways would you be targeting? Why? (5 pts.) 陈志成部分 4. (A) When your fingertips were accidentally hit by a hammer, please describe the molecular mechanism involved in nociception to trigger the pain signaling from peripheral nerve terminals to spinal cord (6 pts.) (B) After the hammer-hit, what efforts you can do to temporally reduce pain without taking drugs and why that efforts can work. (4 pts.) 5. (A) What is neuropathic pain? (1 pt.) (B) Please design a strategy to control neuropathic pain after spinal cord injury and explain why it will work. (4 pts.) (C) Axon regeneration is a major problem after spinal cord injury. However, recent studies have made great progress in axon regeneration in the CNS. Please state why axon regeneration is difficult after spinal cord injury and what are the possible ways to deal with it. (5 pts.) --

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