A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS
A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS
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DOI：
10.1113/jphysiol.2008.159905
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发表时间：
2008-12-01
影响因子：
5.5
通讯作者：
Rothwell, John C.
中科院分区：
文献类型：
--
作者：
Cheeran, Binith;Talelli, Penelope;Rothwell, John C.
脑源性神经营养因子基因（BDNF）被认为是影响成人大脑突触可塑性的众多基因之一，在正常人群中显示出常见的单核苷酸多态性（BDNF Val66Met），与海马体积和情景记忆的差异有关。它也被认为影响了简单的运动学习任务后运动皮层可能的突触变化。在这里，我们通过使用新的无创经颅磁刺激（TMS）和经颅直流电刺激（TDCS）技术来扩展这些研究，这些技术直接测试了静止状态下人类运动皮层神经元回路的兴奋性和可塑性。我们研究了BDNF多态性是否对TMS可塑性探针的易感性有显著影响。将Val66Met携带者与Val66Val个体配对，并在以下方案下进行测试：连续和间歇的θ波脉冲经颅磁刺激；正中神经配对联想刺激；TDCS/ 1hz rTMS模型的稳态可塑性。Met等位基因携带者的反应与Val66Val个体的反应相比，在所有方案中存在显著差异。我们认为这是由于BNDF对突触进行LTP/LTD的易感性的影响。这里测试的神经回路与运动障碍（如肌张力障碍）的病理生理学有关，并被评估为治疗中风的潜在新靶点。因此，多态性可能是影响大脑对损伤和疾病的自然反应的一个因素。
The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synaptic plasticity in the adult brain and shows a common single nucleotide polymorphism (BDNF Val66Met) in the normal population that is associated with differences in hippocampal volume and episodic memory. It is also thought to influence possible synaptic changes in motor cortex following a simple motor learning task. Here we extend these studies by using new non-invasive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) techniques that directly test the excitability and plasticity of neuronal circuits in human motor cortex in subjects at rest. We investigated whether the susceptibility to TMS probes of plasticity is significantly influenced by the BDNF polymorphism. Val66Met carriers were matched with Val66Val individuals and tested on the following protocols: continuous and intermittent theta burst TMS; median nerve paired associative stimulation; and homeostatic plasticity in the TDCS/1 Hz rTMS model. The response of Met allele carriers differed significantly in all protocols compared with the response of Val66Val individuals. We suggest that this is due to the effect of BNDF on the susceptibility of synapses to undergo LTP/LTD. The circuits tested here are implicated in the pathophysiology of movement disorders such as dystonia and are being assessed as potential new targets in the treatment of stroke. Thus the polymorphism may be one factor that influences the natural response of the brain to injury and disease.