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Why do Infants and Children Recover from Nerve Injury Better than Adults? Differential Expression of Acetylcholine Receptor Subunits and Localization of Motor Endplates
Luigi Porciuncula Gonzales, BS; Vivian Chen, BS; Arjun T Gupta, N/A; Tyler R Johnston, MD; Oswald Steward, PhD
University of California, Irvine, Irvine, CA

Introduction: It is widely recognized that there is a difference in how adult and pediatric patients respond and recover after a brachial plexus injury or traumatic nerve injuries. To date, there is no clear understanding as to the etiology for this differential response to neural injury. As nerve injuries induce Wallerian degeneration and initiate degradation of the target end-organ motor endplates (MEPs), it is our hypothesis that there is a differential expression in MEP morphology, subunit composition and distribution between adult and children that may account for their differential response to injury.
Materials and Methods: To assess this, an animal model was used to harvest whole leg and tibialis anterior (TA) muscles from neonatal and adult mice at weekly intervals following birth through 4 weeks, then at monthly intervals through 4 months (n=24, 3 animal specimens at each time point). Muscle tissue was evaluated for alpha-bungarotoxin (?-BTX) and acetylcholine receptor-gamma (AChR-?) expression with fluorescent microscopy. In addition, Western blot analysis was performed to quantify AChR-? protein expression and compared against Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) control.
Results: The data from this study details that adult vs fetal MEPs differ in subunit composition and morphology. Analysis of MEP morphometry revealed that both mature and immature endplates were present in fetal tissue whereas only mature endplates were present in adults. Mature endplates in fetal animals are less complex than the mature endplates found in adult animals. Moreover, immature endplates were distributed throughout fetal muscle in two patterns: (1) individual endplates adjacent to mature MEPs and (2) clusters of endplates not adjacent to mature MEPs. Importantly, there is also a differential expression and spatial localization of AChR subunit ? between early postnatal and adult animals.
Conclusions: These novel data provide insight into potential pathways that may account for the well-documented differential response to nerve injury across the human lifespan. Accordingly, further investigation is warranted as these findings open new possibilities for adjunct treatment modalities following nerve injury.


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