The Relationship between Body Composition, Fatty Acid Metabolism and Diet in Spinal Muscular Atrophy

Acknowledgments: I.B. received a studentship from SMA Angels Charity. M.B.’s SMA research isfunded by SMA Angels Charity, Muscular Dystrophy UK, Action Medical Research and SMA UK. S.H.P.’s SMA research is funded by SMA Europe and Anatomical Society.Peer reviewedPublisher PD

Dynamic remodelling of synapses can occur in the absence of the parent cell body

<p>Abstract</p> <p>Background</p> <p>Retraction of nerve terminals is a characteristic feature of development, injury and insult and may herald many neurodegenerative diseases. Although morphological events have been well characterized, we know relatively little about the nature of the underlying cellular machinery. Evidence suggests a strong local component in determining which neuronal branches and synapses are lost, but a greater understanding of this basic neurological process is required. Here we test the hypothesis that nerve terminals are semi-autonomous and able to rapidly respond to local stimuli in the absence of communication with their parent cell body.</p> <p>Results</p> <p>We used an isolated preparation consisting of distal peripheral nerve stumps, associated nerve terminals and post-synaptic muscle fibres, maintained in-vitro for up to 3 hrs. In this system synapses are intact but the presynaptic nerve terminal is disconnected from its cell soma. In control preparations synapses were stable for extended periods and did not undergo Wallerian degneration. In contrast, addition of purines triggers rapid changes at synapses. Using fluorescence and electron microscopy we observe ultrastructural and gross morphological events consistent with nerve terminal retraction. We find no evidence of Wallerian or Wallerian-like degeneration in these preparations. Pharmacological experiments implicate pre-synaptic P2X7 receptor subunits as key mediators of these events.</p> <p>Conclusion</p> <p>The data presented suggest; first that isolated nerve terminals are able to regulate connectivity independent of signals from the cell body, second that synapses exist in a dynamic state, poised to shift from stability to loss by activating intrinsic mechanisms and molecules, and third that local purines acting at purinergic receptors can trigger these events. A role for ATP receptors in this is not surprising since they are frequently activated during cellular injury, when adenosine tri-phosphate is released from damaged cells. Local control demands that the elements necessary to drive retraction are constitutively present. We hypothesize that pre-existing scaffolds of molecular motors and cytoskeletal proteins could provide the dynamism required to drive such structural changes in nerve terminals in the absence of the cell body.</p

Widespread tissue hypoxia dysregulates cell and metabolic pathways in SMA

Open Access via the Wiley Jisc Agreement Acknowledgments: SHP, EH‐G, INF, SD’A, and JMC were funded by SMA Europe (SMA UK and Prinses Beatrix Spierfonds). Thanks to Prof Andy Welch for helpful discussions on imaging.Peer reviewedPublisher PD

Survival Motor Neuron (SMN) protein is required for normal mouse liver development

We would like to thank Lucas Fraga who helped with primer design and Alison Thomson for tissue collection. We would also like to acknowledge the Microscopy and Histology Core Facility at the University of Aberdeen for the use of their facilities. SHP is funded by Anatomical Society, Euan MacDonald Centre for Motor Neurone Disease Research and an Elphinstone Scholarship for ES from the University of Aberdeen. THG is funded by SMA Trust (UK SMA Research Consortium award), Muscular Dystrophy UK, and Anatomical Society (PhD Studentship). FM is funded by Medical Research Council, SMA-Europe and the National Institute for Health Research Biomedical Research Centre and Great Ormond Street Hospital Children’s Charity. HZ is funded by SMA-Europe and the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. Corrigendum: Survival Motor Neuron (SMN) protein is required for normal mouse liver development Published online: 10 November 2016 DOI: 10.1038/srep35898Peer reviewedPublisher PDFOthe

A role for spinal cord hypoxia in neurodegeneration

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Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment

Acknowledgments This study is supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London (FM and HZ), the Medical Research Council grant (grant reference MR/L013142/1, FM), SMA-Europe grant (FM and HZ) and Great Ormond Street Hospital Children’s Charity grants (FM and HZ). JEM is supported by Great Ormond Street Hospital Children’s Charity. PS is supported by Bill Marshall Fellowship and The CP Charitable Trust at Great Ormond Street Hospital and UCL. SHP is supported by SMA Trust and Euan MacDonald Centre for Motor Neurone Disease Research.Peer reviewedPublisher PD

A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland

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Tissue quality assessment using a novel direct elasticity assessment device (the E-finger): a cadaveric study of prostatectomy dissection.

INTRODUCTION: Minimally invasive radical prostatectomy (RP) (robotic and laparoscopic), have brought improvements in the outcomes of RP due to improved views and increased degrees of freedom of surgical devices. Robotic and laparoscopic surgeries do not incorporate haptic feedback, which may result in complications secondary to inadequate tissue dissection (causing positive surgical margins, rhabdosphincter damage, etc). We developed a micro-engineered device (6 mm2 sized) [E-finger]) capable of quantitative elasticity assessment, with amplitude ratio, mean ratio and phase lag representing this. The aim was to assess the utility of the device in differentiating peri-prostatic tissue types in order to guide prostate dissection. MATERIAL AND METHODS: Two embalmed and 2 fresh frozen cadavers were used in the study. Baseline elasticity values were assessed in bladder, prostate and rhabdosphincter of pre-dissected embalmed cadavers using the micro-engineered device. A measurement grid was created to span from the bladder, across the prostate and onto the rhabdosphincter of fresh frozen cadavers to enable a systematic quantitative elasticity assessment of the entire area by 2 independent assessors. Tissue was sectioned along each row of elasticity measurement points, and stained with haematoxylin and eosin (H&E). Image analysis was performed with Image Pro Premier to determine the histology at each measurement point. RESULTS: Statistically significant differences in elasticity were identified between bladder, prostate and sphincter in both embalmed and fresh frozen cadavers (p = < 0.001). Intra-class correlation (ICC) reliability tests showed good reliability (average ICC = 0.851). Sensitivity and specificity for tissue identification was 77% and 70% respectively to a resolution of 6 mm2. CONCLUSIONS: This cadaveric study has evaluated the ability of our elasticity assessment device to differentiate bladder, prostate and rhabdosphincter to a resolution of 6 mm2. The results provide useful data for which to continue to examine the use of elasticity assessment devices for tissue quality assessment with the aim of giving haptic feedback to surgeons performing complex surgery