BDNF Val66Met polymorphism alters spinal DC stimulation-induced plasticity in humans

The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence neuronal survival, synaptic plasticity, and neurogenesis. A common single nucleotide polymorphism (SNP) of the BDNF gene due to valine-to-methionine substitution at codon 66 (BDNF Val66Met) in the normal population has been associated with complex neuronal phenotype, including differences in brain morphology, episodic memory, or cortical plasticity following brain stimulation and is believed to influence synaptic changes following motor learning task. However, the effect of this polymorphism on spinal plasticity remains largely unknown. Here, we used anodal transcutaneous spinal direct current stimulation (tsDCS), a novel noninvasive technique that induces plasticity of spinal neuronal circuits in healthy subjects. To investigate whether the susceptibility of tsDCS probes of spinal plasticity is significantly influenced by BDNF polymorphism, we collected stimulus-response curves of the soleus (Sol) H reflex before, during, at current offset, and 15 min after anodal tsDCS delivered at Th11 (2.5 mA, 15 min, 0.071 mA/cm(2), and 64 mC/cm(2)) in 17 healthy, Met allele carriers and 17 Val homozygotes who were matched for age and sex. Anodal tsDCS induced a progressive leftward shift of recruitment curve of the H reflex during the stimulation that persisted for at least 15 min after current offset in Val/Val individuals. In contrast, this shift was not observed in Met allele carriers. Our findings demonstrate for the first time that the BDNF Val66Met genotype impacts spinal plasticity in humans, as assessed by tsDCS, and may be one factor influencing the natural response of the spinal cord to injury or disease.