BDNF Val66Met 基因多态性对视觉剥夺后脑重塑和听觉认知代偿调控机制的多模态 MRI研究

Brain Plasticity is both driven by genetic and environment factors. As an important environment factor, visual deprivation has been proven to cause significant compensation in non-visual cognition and reorganization of both human brain structure and function. Moreover, early studies have shown that BDNF plays important roles in brain development and experience-dependent plasticity, and the expression of BDNF was highly dependent on the visual stimuli. The BDNF Val66Met polymorphism that the valine is replaced by methionine in the position 66 of prodomain induces reduced expression of BDNF mRNA and release of BDNF, which can reshape the structure and function of human brain. However, the effects of BDNF Val66Met polymorphism on the structural and functional reorganization and on the non-visual behaviour of brain after visual deprivation are still unknown. Based on the early studies of our group about the brain structural and functional reorganization in the early blind, and about the modulation of BDNF polymorphisms on the brain structure and function in healthy young people, this project plans to further investigate the modulation effects of BDNF gene polymorphism on the brain plasticity and auditory cognitive compensation in adult individual after visual deprivation using multimodal magnetic resonance imaging. Specifically, we focus on the impacts of BDNF Val66Met polymorphism on the brain structure and function in deprived individuals with different onset, and the causal pathways of BDNF polymorphism->brain plasticity-> auditory cognitive compensation, and the modulation of BDNF polymorphisms on the training effect of the blindness after they underwent short-term auditory spatial recognition training task. The expected findings can improve our understanding about the modulation mechanisms of genetic and environment factors on the brain reorganization after visual deprivation, and may further guide the development of new visual recovery and sensory substitute techniques for people with visual deficit.

人脑可塑性是遗传和环境因素共同作用的结果。视觉剥夺（环境因素）已被证实能引起非视觉认知代偿及人脑结构和功能重塑。另外，早期研究表明BDNF在脑发育和经验依赖脑重塑中起着重要的作用，而它的表达和作用受视觉经验的调控。人类BDNF基因Val66Met突变会导致脑组织BDNF水平减低，从而影响脑结构和功能，然而它对视觉剥夺后脑重塑和认知代偿的影响还不明确。课题组在前期研究盲人脑重塑及BDNF基因多态性对正常人脑结构和功能调控的基础上，拟结合多模态MRI技术，系统研究BDNF基因多态性对盲人听觉认知代偿和脑重塑的调控作用，BDNF基因多态性->盲人脑重塑->听觉认知代偿的调控通路，以及盲人接受短期听觉感知训练后BDNF基因多态性对快速脑功能重塑和认知增强的调控作用。本项目研究结果将有助于增进对遗传与环境因素协同调控脑重塑机制的理解，进而为视力障碍人群的视觉康复方法和感觉替代技术等提供理论基础。

人脑可塑性是遗传和环境因素共同作用的结果。感觉剥夺（例如失明或者失聪）是一种常见的强效环境因素，已被证实能引起感觉认知代偿及人脑结构和功能重塑。早期研究表明脑源性神经营养因子（BDNF）在脑发育和经验依赖脑重塑中起着重要的作用。人类BDNF基因Val66Met突变会导致脑组织BDNF水平减低，从而影响脑结构和功能，然而它对感觉剥夺后脑重塑和认知代偿的影响还不明确。课题组在前期研究感觉剥夺后发生脑重塑及BDNF基因多态性对正常人脑结构和功能调控的基础上，结合多模态MRI技术和遗传学关联研究，系统研究BDNF基因多态性和该基因脑组织表达水平对感觉剥夺所致脑重塑的调控作用。研究发现尽管BDNF rs6265多态性对盲人的脑灰质体积和局部脑活动的重构交互作用比较微弱，BDNF基因在人脑组织的表达水平与盲人脑结构和自发脑活动重构、聋人颞上回功能连接重构、以及长期视听训练的自发脑活动重构存在显著关联，提示BDNF基因脑表达水平可能对人脑感觉剥夺以及训练所致的脑重塑具有调控作用。另外，本研究我们还揭示了盲人感觉皮层之间功能连接独特的重构模式，并发现了数百个与感觉皮层功能连接重构存在显著关联的发育特异性基因和经验特异性基因，它们富集于相对特异的生物过程以及神经细胞类型。本项目研究结果将有助于增进对遗传与环境因素协同调控脑重塑机制的理解，进而为感觉障碍人群的视觉康复方法和感觉替代技术等提供理论基础。