| 脑重大疾病的机理和诊治 |
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| 引用本文： | 熊志奇,徐林,周江宁.脑重大疾病的机理和诊治[J].中国科学院院刊,2016,31(7):765-772. |
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| 作者姓名： | 熊志奇 徐林 周江宁 |
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| 作者单位： | 中国科学院上海生命科学研究院神经科学研究所 上海 200031,中国科学院昆明动物研究所 昆明 650223,中国科学技术大学生命科学学院 合肥 230026 |
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| 基金项目： | 中科院战略性先导科技专项项目（B类）（XDB0200000） |
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| 摘 要： | 脑疾病是我国乃至全球人口健康领域正面临的重大挑战。尽快部署脑疾病研究的中长期战略具有重大意义,将显著提升我国在该领域的国际竞争力,促进相关学科的发展以及新技术和新治疗途径的开发,实现脑疾病的精准医疗。脑疾病的研究正在从分子细胞机理、介观网络机制、生物标记物与分子分型、影像诊断和治疗策略研发等多个层面推进,其中介观网络研究是当前脑科学研究的新焦点,将填补分子细胞机理和宏观疾病症状之间的鸿沟。基于脑疾病的复杂性,非人灵长类动物可能是研究人类脑疾病的最优模型,我国在该领域具有明显优势;而脑疾病的早期诊断和早期干预是脑疾病治疗的关键,我国有丰富的临床资源库,亟需建立国际规范化、全国统一化的采样、处理、分析标准和共享的规则。此外,单细胞和单分子技术是微观研究的新趋势,也是精准医疗的关键技术,在解析复杂脑疾病机理方面具有重要的价值。
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| 关 键 词： | 单细胞技术 非人灵长类模型 介观网络 脑疾病 神经调制技术 |
| 修稿时间： | 2016/6/14 0:00:00 |
Major Brain Diseases:Basic and Clinic Aspects |
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| Xiong Zhiqi,Xu Lin and Zhou Jiangning.Major Brain Diseases:Basic and Clinic Aspects[J].Bulletin of the Chinese Academy of Sciences,2016,31(7):765-772. |
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| Authors: | Xiong Zhiqi Xu Lin and Zhou Jiangning |
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| Institution: | Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China,Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China and School of Life Science and Technology, University of Science and Technology of China, Hefei 230026, China |
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| Abstract: | Brain diseases are critical challenges that need to be addressed by the nation as China are becoming a well-off society with a continuous expanding of the aging population. Pervasive developmental brain disorders, psychiatric disorders and neurodegenerative diseases devastate physical and mental health at different ages, and bring huge burdens to families and society, whereas effective therapeutic strategies are still very limited.Given many of these diseases have been intensively investigated at cellular and molecular levels, there are still huge gap at the circuit level how diseases progress. To circumvent this conundrum, scientists are modeling human diseases on animals with higher similarity to human and unveiling the underlying mechanism at single cell and circuit levels. Advances of optogenetic technology as well as cell-type specific manipulation and labeling approaches make it feasible to couple tracing and recording of different micro-circuits with cognitive, emotional and behavioral functions. Meanwhile, non-human primate (NHP) animals resemble human with higher proximity when compared to rodent or low species, and can be used for the development of disease models, especially those associated with sophisticated cognitive or psychiatric functions. As China has large collections of NHP resources, and the public society shows higher tolerance of research activity using NHP animals, scientists should utilize this advantage to develop NHP disease models, which will cultivate world-wide leadership in both basic and clinic neuroscience. Currently, NHP research centers in Shanghai (ION), Kunming (KIZ) and Beijing are developing brain disease models. Transgenic macaque with overexpressed MECP2 that models human autism spectrum disorder was successfully generated in Shanghai. New imaging techniques and big-data tools should be developed to map neuron connectome of whole NHP brain at both structural and functional levels. Furthermore, genetic modified NHP animal models that mimic disease brains challenge current genetic engineering techniques such as CRISPR/Cas9, which should be further modified to reach higher fidelity and lower expenditure of animals and time. Precision medicine of brain diseases requires dissection of molecular and cellular pathology at single cell level. The emerging singlecell sequencing technology enables whole-genome gene profiling of a single cell, making the dissecting of pathological molecular mechanisms more accurate. Research of brain disease is at a historical critical period, and new breakthroughs demand more united efforts from the government, scientists, doctors and enterprises. There is still considerable space to build new collaboration mechanism among these communities, especially basic scientists and clinic doctors. Although China has the largest population in the world, originated findings using Chinese patient samples still account for a very little portion of the world scientific progress. The development of research power for independent original innovation requires substantial advances on the above challenges, and will define the leadership of Chinese research in the world. |
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| Keywords: | single-cell technology non-human primate model Mesoscopic network brain diseases whole-brain connectome |
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