Park Chang-Hyun, Kim Jungyoon, Namgung Eun, Lee Do-Wan, Kim Geon Ha, Kim Myeongju, Kim Nayeon, Kim Tammy D, Kim Seunghee, Lyoo In Kyoon, Yoon Sujung
Department of Psychiatry, Catholic University of Korea College of MedicineSeoul, South Korea.
Ewha Brain Institute, Ewha Womans UniversitySeoul, South Korea.
Front Hum Neurosci. 2017 Aug 3;11:400. doi: 10.3389/fnhum.2017.00400. eCollection 2017.
Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF) gene resulting in a valine (Val) to methionine (Met) substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes ( = 18) and Met-allele carriers ( = 55). Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity.
Val66Met是人类脑源性神经营养因子（BDNF）基因中一种自然发生的多态性，导致第66位密码子处缬氨酸（Val）被甲硫氨酸（Met）取代，在神经可塑性中起重要作用。虽然此前已经研究了BDNF Val66Met多态性对局部脑结构的影响，但其对基于图的白质结构网络构型的影响尚未得到研究。在本研究中，我们评估了BDNF多态性对基于图的白质结构网络的网络特性和鲁棒性的影响。采用图论研究两组（Val纯合子组，n = 18；Met等位基因携带者组，n = 55）白质纤维束成像得出的结构连通性。虽然两组基因型在包括全局效率、局部效率和模块化等全局网络指标上没有差异，但我们发现BDNF Val66Met多态性对白质结构网络的鲁棒性特性有影响。具体而言，与Val纯合子组相比，Met等位基因携带者组的白质结构网络在靶向去除中心节点时显示出更高的脆弱性。这些发现表明，BDNF Val66Met多态性在神经可塑性方面的核心作用可能与根据基因变异在白质结构网络鲁棒性方面的固有差异有关。此外，可以理解Met等位基因携带者对脑部疾病的易感性更高是由于其白质结构连通性稳定性有限。
