Quezada, M. J. | bioRxiv Science

bioRxiv2024

The Impact of Brain-Derived Neurotrophic Factor rs6265 (Val66Met) Polymorphism on Therapeutic Electrical Stimulation for Peripheral Nerve Regeneration: A Preclinical Study of Therapy-Genotype Interactions

The Impact of Brain-Derived Neurotrophic Factor rs6265 (Val66Met) Polymorphism on Therapeutic Electrical Stimulation for Peripheral Nerve Regeneration: A Preclinical Study of Therapy-Genotype Interactions IntroductionPeripheral nerve injuries (PNIs) significantly impact patient quality of life. Therapeutic electrical stimulation (TES) shows promise in enhancing nerve regeneration, but outcomes vary widely. This study investigates the impact of the rs6265 single nucleotide polymorphism (SNP) on TES efficacy in a preclinical rat model and human stem cell-derived motor neurons. MethodsWild-type (WT) and rs6265 variant rats underwent sciatic nerve transection and received either TES or sham treatment. Muscle reinnervation was assessed through compound muscle action potentials and muscle fiber cross-sectional area. Isogenic human iPSC-derived motor neurons were used to study activity-dependent BDNF secretion. ResultsTES improved muscle reinnervation and fiber size in WT but not rs6265 allele carriers. rs6265 allele carriers exhibited impaired activity-dependent BDNF secretion in vitro. DiscussionThe rs6265 polymorphism influences TES efficacy, highlighting the need for personalized approaches in PNI treatment. These findings suggest that genetic screening could optimize therapeutic outcomes. Clinical RelevanceUnderstanding genetic factors affecting TES response can enhance treatment strategies for PNI, potentially improving patient recovery and reducing outcome variability.

neuroscience↗

bioRxiv2019

Experts, but not novices, exhibit StartReact indicating experts use the reticulospinal system more than novices

Motor skill acquisition utilizes a wide array of neural structures; however, few articles evaluate how the relative contributions of these structures shift over the course of learning. Recent evidence from rodents and songbirds suggests there is a transfer from cortical to subcortical structures following intense, repetitive training. Evidence from humans indicate that the reticulospinal system is modulated over the course of skill acquisition and may be a subcortical facilitator of learning. The objective of this study was to evaluate how reticulospinal contributions are modulated by task expertise. Reticulospinal contributions were assessed using StartReact (SR). We hypothesized that expert typists would show SR during an individuated, keystroke task but SR would be absent in novices. Expert (75.2 {+/-} 9.8 WPM) and novice typists (41.6 {+/-} 8.2 WPM) were evaluated during an individuated, keystroke movements. In experts, SR was present in all fingers (except the middle) but was absent in novices (except the little). Together, these results suggest that experts use reticulospinal contributions more for movement than novices indicating that the reticular formation becomes increasingly important for movement execution in highly trained, skilled tasks even those that require individuated movement of the fingers.

neuroscience↗