Inflammation Sciences Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
Gastroenterology. 2011 Sep;141(3):827-836.e1-3. doi: 10.1053/j.gastro.2011.05.047. Epub 2011 Jul 14.
BACKGROUND & AIMS: Polymorphisms in brain-derived neurotrophic factor (BDNF) can affect brain and behavioral responses. However, little is known about the effects of a single nucleotide polymorphism (SNP) in BDNF, at codon 66 (the Val-Met substitution, detected in approximately 33% of the Caucasian population) on stimulation-induced plasticity in the cortico-bulbar system. We examined whether this SNP influenced outcomes of different forms of neurostimulation applied to the pharyngeal motor cortex.
Thirty-eight healthy volunteers were assessed for corticobulbar excitability after single-pulse, transcranial magnetic stimulation of induced pharyngeal electromyographic responses, recorded from a swallowed intraluminal catheter. Thereafter, volunteers were conditioned with pharyngeal electrical stimulation, or 2 forms of repetitive (1 and 5 Hz) transcranial magnetic stimulation (rTMS). Repeated measurements of pharyngeal motor-evoked potentials were assessed with transcranial magnetic stimulation for as long as 1 hour after the 3 forms of neurostimulation and correlated with SNPs at codon 66 of BDNF (encoding Val or Met).
Pharyngeal electrical stimulation significantly increased the amplitude of motor-evoked potentials in individuals with the SNP that encoded Val66, compared to those that encoded Met66, with a strong GENOTYPE*TIME interaction (F₈,₁₁₂ = 2.4; P = .018). By contrast, there was a significant reduction in latencies of subjects with the SNP that encoded Met66 after 5-Hz rTMS (F₃,₆₀ = 4.9; P = .04). In addition, the expected inhibitory effect of 1-Hz rTMS on amplitude was not observed in subjects with the SNP that encoded Met66 in BDNF (F₇,₁₄₀ = 2.23; P = .035).
An SNP in human BDNF at codon 66 affects plasticity of the pharyngeal cortex to different forms of neurostimulation. Genetic analysis might help select specific forms of neurostimulation as therapeutics for patients with disorders such as dysphagic stroke.
脑源性神经营养因子（BDNF）的多态性可影响大脑和行为反应。然而，人们对 BDNF 密码子 66 位（约 33%的白种人存在的缬氨酸-蛋氨酸取代）单核苷酸多态性（SNP）对皮质-延髓系统刺激诱导可塑性的影响知之甚少。我们研究了这种 SNP 是否影响不同形式的神经刺激应用于咽肌皮质后的结果。
38 名健康志愿者接受单脉冲经颅磁刺激，诱导咽肌肌电图反应，从吞咽腔内导管记录。此后，志愿者接受咽电刺激或 2 种形式的重复（1 和 5 Hz）经颅磁刺激（rTMS）。用经颅磁刺激反复测量咽运动诱发电位，在 3 种神经刺激后长达 1 小时进行，并与 BDNF 密码子 66 位的 SNP（编码缬氨酸或蛋氨酸）相关。
与编码 Met66 的个体相比，编码 Val66 的 SNP 个体的咽电刺激显著增加了运动诱发电位的振幅，且存在很强的基因型-时间交互作用（F₈,₁₁₂ = 2.4；P =.018）。相比之下，编码 Met66 的 SNP 个体在 5-Hz rTMS 后潜伏期显著缩短（F₃,₆₀ = 4.9；P =.04）。此外，在编码 Met66 的 SNP 个体中，1-Hz rTMS 对振幅的预期抑制作用并未观察到（F₇,₁₄₀ = 2.23；P =.035）。
BDNF 密码子 66 位的 SNP 影响咽皮质对不同形式神经刺激的可塑性。遗传分析可能有助于选择特定形式的神经刺激作为吞咽障碍性卒中等疾病的治疗方法。
