Division of Neurology, Department of Medicine, University of Toronto and Krembil Brain Institute, Toronto, Ontario, Canada; Melbourne Neuropsychiatry Centre, The University of Melbourne, Victoria 3010, Australia; Department of Biomedical Engineering, The University of Melbourne, Victoria 3010, Australia.
Division of Neurology, Department of Medicine, University of Toronto and Krembil Brain Institute, Toronto, Ontario, Canada; Dept of Neurophysiology, NIMHANS, Bengaluru, India.
Clin Neurophysiol. 2021 Nov;132(11):2827-2839. doi: 10.1016/j.clinph.2021.07.029. Epub 2021 Sep 1.
While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) can impact neuroplasticity, the influence of BDNF genotype on cortical circuitry and relationship to neuroplasticity remain relatively unexplored in human.
Using individualised transcranial magnetic stimulation (TMS) parameters, we explored the influence of the BDNF Val66Met polymorphism on excitatory and inhibitory neural circuitry, its relation to I-wave TMS (ITMS) plasticity and effect on the excitatory/inhibitory (E/I) balance in 18 healthy individuals.
Excitatory and inhibitory indexes of neurotransmission were reduced in Met allele carriers. An E/I balance was evident, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like ITMS plasticity were greater in Val/Val homozygotes. LTP- but not LTD-like effects were restored in Met allele carriers by increasing stimulus intensity to compensate for reduced excitatory transmission.
The influence of BDNF genotype may extend beyond neuroplasticity to neurotransmission. The E/I balance was evident in human motor cortex, modulated by BDNF and measurable using TMS. Given the limited sample, these preliminary findings warrant further investigation.
These novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex.
虽然先前的研究表明脑源性神经营养因子（BDNF）的单核苷酸多态性（Val66Met）可以影响神经可塑性，但 BDNF 基因型对皮质电路的影响及其与神经可塑性的关系在人类中仍相对未知。
使用个体化经颅磁刺激（TMS）参数，我们探讨了 BDNF Val66Met 多态性对兴奋性和抑制性神经回路的影响，以及它与 I 波 TMS（ITMS）可塑性的关系，以及对 18 名健康个体兴奋性/抑制性（E/I）平衡的影响。
在 Met 等位基因携带者中，神经递质的兴奋性和抑制性指数降低。存在 E/I 平衡，其受 BDNF 影响，Val/Val 纯合子中 E/I 比值较高。长时程增强（LTP-）和抑制（LTD-）样 ITMS 可塑性均在 Val/Val 纯合子中更大。通过增加刺激强度来补偿兴奋性传递的降低，仅在 Met 等位基因携带者中恢复了 LTP-而不是 LTD-样效应。
BDNF 基因型的影响可能超出神经可塑性，延伸至神经传递。E/I 平衡在人类运动皮层中明显存在，受 BDNF 调节，可使用 TMS 测量。鉴于样本有限，这些初步发现值得进一步研究。
这些新发现表明 BDNF 基因型在人类运动皮层的神经回路中具有更广泛的作用。
